Human life is dependent upon the hearts ability to pump forcefully and frequently enough, but heart failure signs can disturb its normal function. Most humans cannot live more than four minutes without a heartbeat or continuous blood-flow. At that time, brain cells begin to die because they lack adequately oxygenated blood-flow.

The human adult body requires, on average, 5.0 liters of re-circulated blood per minute. In the cardiology field, this metric is called the Cardiac Output, which is calculated as Stroke Volume (SV) x Heart Rate (HR). Another key metric is a patients Ejection-Fraction (EF %). A patients EF tells a cardiologist and other physicians if his or her heart is functioning normally or low normally. It is a measurement of ones heart contraction, with a normal EF range being 55-70%.

This number can also be combined with a patients heart rate to provide physicians with a baseline of a patients cardiac status. A normal range for an adult is 60-100 beats per minute, and this can be significantly higher during a normal pregnancy.

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For a cardiologist, cardiac metrics indicate if their services are required and allowthem to sign-off on pre-operative cardiac clearances. For other physicians, it tells them if the organ which they specialize in is being perfused adequately (for example, a nephrologist would be interested to know kidney perfusion). It can also indicate the degree to which decreased heart function may affect the severity or spread of disease.

When the heart fails to contract forcefully enough and its performance decreases to the point where its ability to circulate blood adequately is compromised (the EF% falls below 40%), this is considered heart failure. The clinical parameters of heart failure are clearly defined by the New York Heart Association (NYHA), which places patients in NYHA Class III & IV into the heart failure category.

An echocardiogram (often called an Echo), as opposed to an Electrocardiogram (EKG or ECG), allows technicians and physicians to visualize the beating heart. Video clips of the heart contracting are digitally recorded, and a patients EF and Cardiac Output (CO) can be measured with several diagnostic tools (Fractional Shortening via 2D or M-Mode measurements and Simpsons Method via 2D and 3D Quantification) on a cardiovascular ultrasound system.

When an experienced echo tech or cardiologist views a failing heart, it is immediately apparent. Based on my experience reading echocardiograms, I can see that the heart walls or heart muscles (myocardium) are not contracting as vigorously as they should.

For patients with a 5% EF range, any physical movement is extremely strenuous, and they can go into cardiac arrest at any moment, which is why they are usually on cardiac telemetry in a hospital setting. Most likely, a patient with 5% EF range would be awaiting a heart transplant, unless there is a medical condition preventing them from being eligible.

Once a patient falls into the heart failure range, they will be lethargic and have severe limits on activities. Other clinical manifestations of heart failure can include peripheral edema (i.e. swelling in the feet, legs, ankles, or stomach), pulmonary edema, and shortness of breath. In many cases, this can lead to depression.

In evaluating the frequency of heart failure in the U.S, statistics from the U.S. Centers for Disease Control (CDC) find that approximately 5.7 million adults are afflicted with this condition. Additionally, care for congestive heart failure costs an estimated $30.7B per year. Furthermore, the mortality rates of patients suffering from heart failure indicate its clinical severity, with 1 in 5 patients with this condition dying within a year of receiving the diagnosis.

A patient experiencing severe heart failure has limited treatment options, which are expensive, complicated, and have major lifestyle implications.

These limited options include:

Consequently, physicians need more effective weapons for treating heart failure in order to improve patients lives and reduce healthcare-related costs. CHF patients have disproportionate hospital readmission rates when compared to other major diseases.

Enter in the growing field of cardiac stem cell treatments, which introduce fundamentally new treatment options for heart failure patients. In cardiac stem cell treatments, stem cells are taken from a patients bone marrow or fat tissue in a sterile surgical procedure and injected via a catheter-wire into infarcted or poorly contracting muscular segments of the hearts main pumping chamber, the left ventricle (LV).

Over the course of a few months, the stem cells impact myocardial cells and begin to improve the contractility of the affected segments, most likely through paracrine signaling mechanisms and impacting the local microenvironment. This can bring a patients EF to low-normal or even normal levels. As a result, a patient can live a more normal life and return to many activities.

A very early clinical trial aimed at evaluating the potential and effectiveness of cardiac stem cell therapy in humans was conducted in 2006 utilizing a commercial product, VesCellTM. The parameters and results of this trial were documented in the American Heart Associations Circulation, Abstract 3682: Treatment of Patients with Severe Angina Pectoris Using Intracoronarily Injected Autologous Blood-Borne Angiogenic Cell Precursors.The subjects of this trial received an intracoronary injection of VesCellTM, an Autologous Angiogenic Cell Precursor (ACP)-based product.

The authors drew their conclusion regarding this study. VesCell therapy for chronic stable angina seems to be safe and improves anginal symptoms at 3 and 6 months. Larger studies are being initiated to evaluate the benefit of VesCell for the treatment of this and additional severe heart diseases. (Source: Tresukosol et al. Abstract 3682: Treatment of Patients with Severe Angina Pectoris Using Intracoronarily Injected Autologous Blood-Borne Angiogenic Cell Precursors. Circulation. October 31, 2006. Vol. 114, Issue Suppl 18. Link: http://circ.ahajournals.org/content/114/Suppl_18/II_786.4 )

Another early cardiac stem cell clinical trial was performed in 2009 by a Cedars-Sinai team based on technologies and discoveries made by Eduardo Marban, MD, PhD, and led by Raj Makkar, MD. In this study, they explored the safety of harvesting, expanding, and administering a patients cardiac stem cells to repair heart tissue injured by myocardial infarction.

Recently, the American College of Cardiology (ACC) also announced results of a ground-breaking clinical study to evaluate the efficacy and effectiveness of cardiac stem cell treatment for heart failure patients. As stated by Timothy Henry, M.D., Director of Cardiology at Cedars-Sinai Heart Institute and one of the studys lead authors, This is the largest double-blind, placebo-controlled stem cell trial for treatment of heart failure to be presentedBased on these positive results, we are encouraged that this is an attractive potential therapy for patients with class III and class IV heart failure.

Additionally, Dr. Charles Goldthwaite, Jr, published a whitepaper titled, Mending a Broken Heart: Stem Cells and Cardiac Repair, in which he draws the conclusion, Given the worldwide prevalence of cardiac dysfunction and the limited availability of tissue for cardiac transplantation, stem cells could ultimately fulfill a large-scale unmet clinical need and improve the quality of life for millions of people with CVD. However, the use of these cells in this setting is currently in its infancymuch remains to be learned about the mechanisms by which stem cells repair and regenerate myocardium, the optimal cell types, and modes of their delivery, and the safety issues that will accompany their use.

Clearly, there is a trend toward acceptance of cardiac stem cell therapies as an emerging treatment option. Several world-renowned institutes are now conducting clinical studies involving cardiac stem cell treatment, as well as applying for intellectual property protection (patents) pertaining to the techniques required in administrating the therapies.

The key questions at this point in time appear to be:

An important whitepaper pertaining to cardiac stem cells is Ischemic Cardiomyopathy Patients Treated with Autologous Angiogenic and Cardio-Regenerative Progenitor Cells, written by Dr. Athina Kyritsis, et al. In it, the physicians describe their objective as investigating the feasibility, safety, and clinical outcome of patients with Ischemic Cardiomyopathy treated with Autologous Angiogenic and Cardio-Regenerative Progenitor cells (ACPs).

The researchers state: In numerous human trials there is evidence of improvement in the ejection fractions of Cardiomyopathy patients treated with ACPs. Animal experiments not only show improvement in cardiac function, but also engraftment and differentiation of ACPs into cardiomyocytes, as well as neo-vascularization in infarcted myocardium. In our clinical experience, the process has shown to be safe as well as effective.

The authors also found that patients treated with this approach gained increases in cardiac ejection fraction from their starting measurements, with improvements in their cardiac ejection fraction of 21 points (75% increase) at rest and 28.5 points (80% increase) at stress. As a result of these finding, the authors conclude, ACPs can improve the ejection fraction in patients with severely reduced cardiac function with benefits sustained to six months.

In the practice of medicine, the focus should be on delivering excellent care to patients. If there are cardiac stem cell treatments available, then regulatory obstacles should be removed when sufficient clinical trial evidence has been provided to indicate safety and efficacy.

Cardiologist Zannos Grekos, MD, a pioneer in cardiac stem cell therapy since 2006, points to the vastly untapped promise of related therapies, commenting Those of us that have been involved with cardiac stem cell treatment for the last 10-plus years can see the incredible potential this approach has.

As of 2017, the U.S. healthcare system is under enormous pressure to deliver affordable healthcareto a growing population of patients, especially those who are fully or partially covered under Medicare or Medicaid (many have secondary coverage). Although we are in the infancy of its development, cardiac stem cell treatments represent a potentially powerful treatment alternative to patients with heart failure symptoms.

To learn more, view the resources below.

1) Regenocyte http://www.regenocyte.com

2) Cleveland Clinic Stem Cell Therapy for Heart Disease my.clevelandclinic.org/health/articles/stem-cell-therapy-heart-disease

3) Harvard Stem Cell Institute (HSCI) hsci.harvard.edu/heart-disease-0

4) Cedars Sinai Cardiac Stem Cell Treatment http://www.cedars-sinai.edu/Patients/Programs-and-Services/Heart-Institute/Clinical-Trials/Cardiac-Stem-Cell-Research.aspx

5) Johns Hopkins Medicine Cardiac Stem Cell Treatments http://www.hopkinsmedicine.org/stem_cell_research/cell_therapy/a_new_path_for_cardiac_stem_cells.html

What do you think about heart failure signs and cardiac stem cell therapies? Share your thoughts in the comments section below.

Up Next:European Society of Cardiology (ESC) Congress Presentation Reveals Results From Pre-Clinical Study Using CardioCells Stem Cells for Acute Myocardial Infarction

Guest Post: This is a guest article by Clifford M. Thornton, a Certified Cardiovascular Technologist, experienced Echocardiographer Technician, and journalist in the cardiac and medical device fields. His articles have been published in Inventors Digest, Global Innovation Magazine, and Modern Health Talk. He is enthusiastic about progress with cardiac stem cell therapies and their role in heart failure treatment.He can be reached byphone at 267-524-7144 or by email at[emailprotected].

Editors Note This post was originally published on March 14, 2017, and has been updated for quality and relevancy.

Heart Failure Signs | Cardiac Stem Cell Therapies for Heart Failure Treatment

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SC21 BioTech: Stem Cell Skin Care Set

SC21 nowoffers a rejuvenating stem cell skin careset that is available to help restore aging skin. At SC21, we have been able to combine human mesenchymal stem cell growth factors, polypeptide complexes, and cytokines, with our day time anti-aging cream & evening hydration serum.

Our SC21 biotechnology scientists have developed a process to isolate potent rejuvenating factors from human stem cells. By resupplying the skin with these powerful missing factors, SC21 Day & Night Stem Cell Skin Care promotes cell renewal, boosts the production of collagen and elastin, restores aging cells, and, ultimately, provides you with more youthful looking skin.

It is important to note that as we age, the stem cell population that is vital in providing healing signals to the skin dramatically diminishes. As a result of this, the rejuvenating components the skin needs to maintain its appearance lessen. By replenishing lost peptides, cytokines & growth factors with the use of a topical product on the skin, we, through the day &night skin care set, are able to effectively re-engage the skins healing process.

The SC21 day & night stem cell skin care rejuvenation set also has a complete solution for restoring aging skin. We have, through the day anti-aging cream & night hydration serum been able to use: human mesenchymal stem cell growth factors, to regenerate human tissues; polypeptide complexes, (which penetrate the epidermis, outer layer of our skin) to send signals to the skin cells and cytokines proteins to send signals between the skin cells.

Focus Ingredient of Growth Factor Skin Care:

Mesenchymal Stem Cell (MSC) Peptide Complex = 15% (cytokines, growth factors, peptide complex)

Other Key Ingredients:

Focus Ingredient of Growth Factor Skin Care:

Mesenchymal Stem Cell (MSC) Peptide Complex = 20%(cytokines, growth factors, peptide complex)

Other Key Ingredients:

Apply 2-3 pumps to clean & dry skin.

Peptides are easier explained as signaling molecules produced by cells to instruct other cells.

As cellular messengers, cytokines influence and control our biological processes from start to finish. There are hundreds of unique cytokines in the human body. Cells talk with cytokines to repair injury, repel microbes, fight infections, and develop immunity.

Growth factors, are, on the other hand, diffusible signaling proteins that stimulate the growth of specific tissues and play a crucial role in promoting cell differentiation and division.

Many modern medical advances, including stem cell breakthroughs, are made possible due to our growing understanding of cytokines & growth factors. We use modern culture techniques (the same type used to produce human insulin and other naturally occurring substances) to grow human stem cells in the laboratory to harvest their regenerative cytokines and growth factors.

Mesenchymal stem cells (MSCs), which are traditionally found in the bone marrow, are used to improve function upon integration because they are self-renewing cells that have the capacity to differentiate, and are capable of replacing and repairing damaged tissues.

MSCs can consequently during culture, produce the following:

Our skin cells are biologically designed to continuously renew themselves, but, starting from our mid 20s, the skin cell renewal process slows down and our skin becomes thinner. This thinning causes us to be more prone to skin damage from external elements.

However, there are other factors that can contribute to our aging process, and in other cases even cause premature aging. Some of these factors include:

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Stem Cell Skin Care - anti-aging cream and hydration Serum

Skin Stem Cells Comments Off on Stem Cell Skin Care – anti-aging cream and hydration Serum | November 14th, 2018

Marc Darrow MD, JD. Thank you for reading my article. You can ask me your questions aboutthis articleusing the contact form below.

I want to begin this article with a case study from our recently published research in theBiomedical Journal of Scientific & Technical Research.

Afterphysical assessment of her lower back, we determinedher pain was generated from a lumbosacral sprain. Not the narrowing of the L1-L5,S1

She had oneBone marrow derived stem cell treatment and at first follow up two weeks after the injections,the patient experienced no pain or stiffness and reported 90% total improvement. Approximately a year after treatment, she felt evenbetter, and stated that she was able to perform aerobics and line dancing for an hour and a half a day with no pain. She reportedinfrequent stiffness, but not as severe as it was prior to treatment.

Her resting and active pain were 0/10 and functionality score was 39/40.(1)

This was one document case in the medical literature. Over the years we have helped many people avoid a stenosis surgery they did not want or possibly did not even need.

Despite the fact that many studies insist that surgical treatment is the best option for lumbar spinal stenosis, a startling study was published in the medical journal Spine. In this study, American, Canadian and Italian researchers published their evidence:

We have very little confidence to conclude whether surgicaltreatmentor a conservative approach is better forlumbarspinal stenosis, and we can provide no new recommendations to guide clinical practice. . .However, it should be noted that the rate of side effects ranged from 10% to 24% in surgical cases, and no side effects were reported for any conservativetreatment. (2)

In the above research it should be pointed out the comparison between lumbar surgery and conservative treatments did not include stem cell therapy. They included the traditional conservative treatments including physical therapy, cortisone injections, pain medications and others listed below.

One of the reasons surgery may be no better than conservative care is that the surgery tried to fix a problem that was not there: Pain.

In the medical journal Osteoarthritis and Cartilage,doctors reported that many asymptomatic individuals, those with no pain or other challenges, have radiographic lumbar spinal stenosis. In other words they only have lumbar spinal stenosis on the MRI.

The doctors noted:

A diagnosis of spinal stenosis can be frightening because of the implications that a surgery may be needed to avoid paralysis.It is important to note that in instances where stenosis is so severe that the patient has lost circulation to the legs or bladder control a surgical consult should be made immediately.

In the December 2017 edition of the medical journal Spine, doctors from the University of Pittsburgh and University Toronto reported these observations in patients seeking non-surgical treatments for lumbar spinal stenosis.

Individuals with lumbar spinal stenosis may believe misinformation and information from non-medical sources, especially when medical providers do not spend sufficient time explaining the disease process and the reasoning behind treatment strategies. Receiving individualized care focused on self-management led to fewer negative emotions toward care and the disease process. Clinicians should be prepared to address all three of these aspects when providing care to individuals with lumbar spinal stenosis.(4)

Back pain can certainly cause anxiety, depression, and catastrophizing thoughts. The people in this study wanted education and involvement in their choice of treatment. I hope I can provide some for you here in this article.

Lumbar Spinal Stenosis is a narrowing of the space between vertebrae where the spinal cord and the spinal nerves travel. It is a diagnostic term to describe lower back pain with or without weakness and loss of sensation in the legs. It is a very common condition brought on mostly by aging and the accompanying degeneration of the spine.

In the recommended surgical procedures for spinal stenosis, two choices are the most favored.

A paper published in October 2017 gives a good outline where conservative medicine is in the treatment of Lumbar stenosis. It is from doctors at the University of South Carolina

This is indeed a fair assessment of SOME of the treatment options available to patients.However, not all doctors agree. At New York University in June 2017 research, doctors wrote:

The highest levels of evidence do not support minimally invasive surgery over open surgery for cervical orlumbardisc herniation. However, minimally invasive surgery fusion demonstrates advantages along with higher revision and hospital readmission rates. These results should optimize informed decision-making regarding minimally invasive surgery versus open spine surgery, particularly in the current advertising climate greatly favoring minimally invasive surgery.(6)

Researchers at theUniversity of Sydneysay that the evidence for recommending lumbar spinal surgery as the best option to patients is lacking and it is possible that a sham or placebo surgery can deliver the same results.(7)

In the research I cited at the top of this article, doctors at the Italian Scientific Spine Institute in Milanwrote: We cannot conclude on the basis of this review whether surgical or nonsurgical treatment is better for individuals with lumbar spinal stenosis. We can however report on the high rate of effects reported in three of five surgical groups and that no side effects were reported for any of the conservative treatment options.(8)

Considering the majority of these procedures are unnecessarily being performed for degenerative disc disease alone, spine surgeons should be increasingly asked why they are offering these operations to their patients

Ateam of Japanese researchers found thatpatients with lumbar spinal stenosiswho do not improve after nonsurgical treatments are typically treated surgically using decompressive surgeryand spinal fusion surgery. Unfortunately the researchers could not determine if the surgery had any benefit either.(9)Maybe the patients problem was not the stenosis?

Now lets go to another paper that has more of an opinion: From Dr. Nancy Epstein ofWinthrop University Hospital:

Surgeons at Leiden University Medical Centre in the Netherlandsspeculate that doctors go into a diagnosis oflumbar spinal stenosis with the thought that there is osteoarthritis a bony overgrowth on the spinal nerves. Once determined, the symptoms of patients can be categorized into two groups; regional (low back pain, stiffness, and so on) or radicular (spinal stenosis mainly presenting as neurogenic claudication nerve inflammation).

In the patients who primarily complain of radiculopathy (radiating leg pain) with an stable spine, a decompression surgery may be recommendedto removebonefrom around thenerve root to give the nerve root more space.The surgeons warn of thefear that surgery to a stable spine will make it unstable.(11)

Afusion procedure to limit the movement between two vertebrae and hopefully stop the compression of nerves is another option. As mentioned by independent research above surgery for spinal stenosis should onlybe considered after conservative therapies have been exhausted.Surgical treatment of lumbar spinal disorders, including fusion, is associated with a substantial risk of intraoperative and perioperative complications,as pointed out in the research by surgeons from Catholic University in Rome.(12)

Bone growth occurs in the spine because the bone is trying to stabilize the spine from excessive movement or laxity. Fusion surgery is recommended as a means to accelerate that type of stabilization. Regenerative medicine includingPRP andStem Cell Therapy(watch the video)works in a completely different way. Theystabilize the spine by strengthening the often forgotten and underappreciated spinal ligaments and tendons.These techniques help stabilize the spine, which is imperative as unstable joints can lead to or further exacerbate the arthritis that causes spinal stenosis.

In the medical journal Insights into imaging, researchers wrote of the four factors associated with the degenerative changes of the spine that cause spinal canal stenosis:

The same research suggests that these conditions can prevent the formation of new tissue (collagen) which can initiate repair.(13)

Collagen is of course the elastic material of skin and ligaments. Here the association between collagen interruption and spinal stenosis can be made to show spinal instability can be THE problem of symptomatic stenosis.

A fascinating study on what damaged spinal ligaments can do

A fascinating study in the Asian Spine Journal investigated the relationship between ligamentum flavum thickening and lumbar segmental instability, disc degeneration, and facet joint osteoarthritis. Ligament thickening is the result of chronic inflammation. Chronic ligament inflammation is the result of a ligament injury that is not healing.

What these researchers found was a significant correlation between ligamentum flavum thickness, spinal instability and disc degeneration. More so, the worse the degenerative disc disease, the worse the ligamentum flavum thickness.(14)

PRP and stem cells address the problem of ligament damage and inflammation. Addressing these problems address the problems of spinal instability. Addressing the problems of spinal instability can address the problems of spinal and cervical stenosis.

A leading provider of bone marrow derived stem cell therapy, Platelet Rich Plasma and Prolotherapy11645 WILSHIRE BOULEVARD SUITE 120, LOS ANGELES, CA 90025

PHONE: (800) 300-9300

1 Darrow M, Shaw BS. Treatment of Lower Back Pain with Bone Marrow Concentrate. Biomed J Sci&Tech Res 7(2)-2018. BJSTR. MS.ID.001461. DOI: 10.26717/ BJSTR.2018.07.001461.

2 Zaina F, TomkinsLane C, Carragee E, Negrini S. Surgical versus nonsurgical treatment for lumbar spinal stenosis. The Cochrane Library. 2016 Jul 1.

3 Lynch AD, Bove AM, Ammendolia C, Schneider M. Individuals with lumbar spinal stenosis seek education and care focused on self-managementresults of focus groups among participants enrolled in a randomized controlled trial. The Spine Journal. 2017 Dec 12

4 Ishimoto Y, Yoshimura N, Muraki S, Yamada H, Nagata K, Hashizume H, Takiguchi N, Minamide A, Oka H, Kawaguchi H, Nakamura K. Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study. Osteoarthritis and cartilage. 2013 Jun 1;21(6):783-8.

5Patel J, Osburn I, Wanaselja A, Nobles R. Optimal treatment for lumbar spinal stenosis: an update. Current Opinion in Anesthesiology. 2017 Oct 1;30(5):598-603.

6 Vazan M, Gempt J, Meyer B, Buchmann N, Ryang YM. Minimally invasive transforaminal lumbar interbody fusion versus open transforaminal lumbar interbody fusion: a technical description and review of the literature. Acta Neurochir (Wien). 2017 Jun;159(6):1137-1146

7Machado GC, Ferreira PH, Yoo RI, et al. Surgical options for lumbar spinal stenosis. Cochrane Database Syst Rev. 2016 Nov 1;11:CD012421.

8Zaina F, Tomkins-Lane C, Carragee E, Negrini S. Surgical Versus Nonsurgical Treatment for Lumbar Spinal Stenosis. Spine (Phila Pa 1976). 2016 Jul 15;41(14):E857-68.

9 Inoue G, Miyagi M, Takaso M. Surgical and nonsurgical treatments for lumbar spinal stenosis. Eur J Orthop Surg Traumatol. 2016 Oct;26(7):695-704. doi: 10.1007/s00590-016-1818-3. Epub 2016 Jul 25.

10 Epstein NE. More nerve root injuries occur with minimally invasive lumbar surgery: Lets tell someone. Surg Neurol Int. 2016 Jan 25;7(Suppl 3):S96-S101. doi: 10.4103/2152-7806.174896. eCollection 2016.

11Overdevest GM, Moojen WA, Arts MP, Vleggeert-Lankamp CL, Jacobs WC, Peul WC.Management of lumbar spinal stenosis: a survey among Dutch spine surgeons. Acta Neurochir (Wien). 2014 Aug 7. [Epub ahead of print]

12.Proietti L, Scaramuzzo L, Schiro GR, Sessa S, Logroscino CA. Complications in lumbar spine surgery: A retrospective analysis. Indian J Orthop. 2013 Jul;47(4):340-5. doi: 10.4103/0019-5413.114909.

13 Kushchayev SV, Glushko T, Jarraya M, et al. ABCs of the degenerative spine.Insights into Imaging. 2018;9(2):253-274. doi:10.1007/s13244-017-0584-z.

14 Yoshiiwa T, Miyazaki M, Notani N, Ishihara T, Kawano M, Tsumura H. Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis.Asian Spine Journal. 2016;10(6):1132-1140. doi:10.4184/asj.2016.10.6.1132.2373

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Spinal Cord Stem Cells Comments Off on Stem cells for stenosis – Dr. Marc Darrow is a Stem Cell … | October 14th, 2018

With patches of stem cells on their broken spinal cords, partially paralyzed rats once againreached out and grabbed distant treats, researchers report in Nature Medicine.

While previous studies have shown progress in regenerating certain types of nerve cells in injured spinal cords, the study is the first to coax the regrowth of a specific set of nerve cells, called corticospinal axons. These bundles of biological wiring carry signals from the brain to the spinal cord and are critical for voluntary movement. In the study, researchers were able to use stem cells from rats and humans to mend the injured rodents.

The corticospinal projection is the most important motor system in humans, senior author Mark Tuszynski at the University of California, San Diego said. It has not been successfully regenerated before. Many have tried, many have failedincluding us, in previous efforts.

For the study, the researchers used rat and human neural progenitor cells, which can produce several different types of cells found in the central nervous system. The researchers coaxed the cells into forming spinal cord tissue using specific chemical signals. When injected into the damaged spinal cords of rats, the cells took root, filling lesions with new tissue and corticospinal axons. And the new nerve cells linked up with the severed connections left hanging from the injury, allowing signals to traverse the patch.

In mobility tests, injured rats that got the spinal patch could better stretch out their front legs to grab hard-to-reach treats compared with injured rats without the stem-cell grafts.

Still, the cord-patching method is far from clinical use in humans, the authors caution. Researchers will need to follow the rats to look at long-term safety and effectiveness of the patches. Then, they'll have to try out the patches in other animal models before optimizing the method for humans.

But,Tuszynski said, "now that we can regenerate the most important motor system for humans, I think that the potential for translation is more promising."

Nature Medicine, 2015. DOI: 10.1038/nm.4066 (About DOIs).

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Scientists regenerate spinal cord in injured rats with ...

Spinal Cord Stem Cells Comments Off on Scientists regenerate spinal cord in injured rats with … | September 28th, 2018

Are there enough stem cells in your knees to heal the damage of osteoarthritis? If yes, why arent those stem cells fixing your knees now? Is it a lack of numbers?

Marc Darrow MD, JD. Thank you for reading my article. You can ask me your questions about bone marrow derived stem cells using the contact form below.

In 2011, doctors at the University of Aberdeen published research in the journal Arthritis and rheumatism that provided the first evidence that resident stem cells in the knee joint synovium underwent proliferation (multiplied) and chondrogenic differentiation (made themselves into cartilage cells) following injury.(1)

If the stem cells in your knee synovial lining are abundant and have the ability to rebuild cartilage after injury, why isnt your knee fixing itself?

One of those 40 studies was performed by researchers at theUniversity of Calgary in 2012. Among their questions, if the stem cells in the knee synovial lining are abundant and have the ability to rebuild cartilage after injury, why isnt the knee fixing itself? Here is what they published:

Since osteoarthritis leads to a progressive loss of cartilage and synovial progenitors (rebuilding) cells have the potential to contribute to articular cartilage repair, the inability of osteoarthritis synovial fluid Mesenchymal progenitor cells (stem cell growth factors) to spontaneously differentiate into chondrocytes suggests that cell-to-cell aggregation and/or communication may be impaired in osteoarthritis and somehow dampen the normal mechanism of chondrocyte replenishment from the synovium or synovial fluid. Should the cells of the synovium or synovial fluid be a reservoir of stem cells for normal articular cartilage maintenance and repair, these endogenous sources of chondro-biased cells would be a fundamental and new strategy for treating osteoarthritis and cartilage injury if this loss of aggregation & differentiation phenotype can be overcome.(2)

This research was supported in anew study from December 2017 In Nature reviews. The paper suggested that recognizing that joint-resident stem cells are comparatively abundant in the joint and occupy multiple niches (from the center of the joint to the out edges) will enable the optimization of single-stage therapeutic interventions for osteoarthritis.(3) The idea is to get these native stem cells to repair.

Now we know that there are many stem cells in the knee, when there is an injury there are more stem cells. If we can figure out how to get these stem cells turned on to the healing mode, the knee could heal itself of early stage osteoarthritis. So the problem is not the number of stem cells, BUT, communication.

This failure to communicate was also seen in other research. In 2016, another heavily cited paper, this time fromTehran University for Medical Sciences, noted that despite their larger numbers,the native stem cells act chaotically and are unable to regroup themselves into a healing mechanism and repair the bone, cartilage and other tissue. Introducing bone marrow stem cells into this environmentgets the native stem cells in line and redirects them to perform healing functions. The joint environmentis changed from chaotic to healing because of communication.(4) It should be pointed out that at the time of this article update (August 2018) 62 medical studies cited the research in this papers findings).

A recentpaper from a research team inAustralia confirms how this change of joint environment works. It starts with cell signalling a new communication network is built.

University of Iowa research published in theJournal of orthopaedic research

Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous (from you, not donated) stem/progenitor cells has emerged as a promising new strategy.

(The research team) showed previously that migratory chondrogenic progenitor cells (mobile cartilage growth factors) were recruited to injured cartilage, where they showed a capability in situ (on the spot) tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells.

Explant studies revealed that migrating cells were mainly confined to the red zone (where the blood is and its growth factors) in normal menisci: However, these cells were capable of repopulating defects made in the white zone (the desert area where no blood flows. Migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. (They were ready to heal) Gene expression profiling showed that the migrating population was more similar tochondrogenic progenitor cells (mobile cartilage growth factors) than other meniscus cells. Finally, migrating cells equaledchondrogenic progenitor cells in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential.(6)

The intrinsic progenitor cell population with strong reparative potential are in your knee waiting to be mobilized.

So what are we to make of this research?There are a lot of stem cells in a knee waiting to repair. The problem is they are confused and not getting the correct instructions. Bone marrow stem cell therapy can fix the communication problem and begin the repair process anew.

A leading provider of bone marrow derived stem cell therapy, Platelet Rich Plasma and Prolotherapy11645 WILSHIRE BOULEVARD SUITE 120, LOS ANGELES, CA 90025

PHONE: (800) 300-9300

1 Kurth TB, Dellaccio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum. 2011 May;63(5):1289-300. doi: 10.1002/art.30234.

2 Krawetz RJ, Wu YE, Martin L, Rattner JB, Matyas JR, Hart DA. Synovial Fluid Progenitors Expressing CD90+ from Normal but Not Osteoarthritic Joints Undergo Chondrogenic Differentiation without Micro-Mass Culture. Kerkis I, ed.PLoS ONE. 2012;7(8):e43616. doi:10.1371/journal.pone.0043616.

3 McGonagle D, Baboolal TG, Jones E. Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nature Reviews Rheumatology. 2017 Dec;13(12):719.

4Davatchi F, et al. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis. 2016 Mar;19(3):219-25.

5. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A.Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy a review.BMC Musculoskelet Disord. 2016 May 26;17(1):230. doi: 10.1186/s12891-016-1085-9. Review.

6 Seol D, Zhou C, et al. Characteristics of meniscus progenitor cells migrated from injured meniscus. J Orthop Res. 2016 Nov 3. doi: 10.1002/jor.23472.

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Embryonic stem cells (ES cells or ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo.[1][2] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. Isolating the embryoblast, or inner cell mass (ICM) results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage should have the same moral considerations as embryos in the post-implantation stage of development.[3][4] Researchers are currently focusing heavily on the therapeutic potential of embryonic stem cells, with clinical use being the goal for many labs. These cells are being studied to be used as clinical therapies, models of genetic disorders, and cellular/DNA repair. However, adverse effects in the research and clinical processes have also been reported.

Embryonic stem cells (ESCs), derived from the blastocyst stage of early mammalian embryos, are distinguished by their ability to differentiate into any cell type and by their ability to propagate. It is these traits that makes them valuable in the scientific/medical fields. ESC are also described as having a normal karyotype, maintaining high telomerase activity, and exhibiting remarkable long-term proliferative potential.[5]

Embryonic stem cells of the inner cell mass are pluripotent, meaning they are able to differentiate to generate primitive ectoderm, which ultimately differentiates during gastrulation into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult human body. Pluripotency distinguishes embryonic stem cells from adult stem cells, which are multipotent and can only produce a limited number of cell types.

Under defined conditions, embryonic stem cells are capable of propagating indefinitely in an undifferentiated state. Conditions must either prevent the cells from clumping, or maintain an environment that supports an unspecialized state.[2] While being able to remain undifferentiated, ESCs also have the capacity, when provided with the appropriate signals, to differentiate (presumably via the initial formation of precursor cells) into nearly all mature cell phenotypes.[6]

Due to their plasticity and potentially unlimited capacity for self-renewal, embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Pluripotent stem cells have shown potential in treating a number of varying conditions, including but not limited to: spinal cord injuries, age related macular degeneration, diabetes, neurodegenerative disorders (such as Parkinson's disease), AIDS, etc.[7] In addition to their potential in regenerative medicine, embryonic stem cells provide an alternative source of tissue/organs which serves as a possible solution to the donor shortage dilemma. Not only that, but tissue/organs derived from ESCs can be made immunocompatible with the recipient. Aside from these uses, embryonic stem cells can also serve as tools for the investigation of early human development, study of genetic disease and as in vitro systems for toxicology testing.[5]

According to a 2002 article in PNAS, "Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering."[8]

However, embryonic stem cells are not limited to cell/tissue engineering.

Current research focuses on differentiating ESCs into a variety of cell types for eventual use as cell replacement therapies (CRTs). Some of the cell types that have or are currently being developed include cardiomyocytes (CM), neurons, hepatocytes, bone marrow cells, islet cells and endothelial cells.[9] However, the derivation of such cell types from ESCs is not without obstacles, therefore current research is focused on overcoming these barriers. For example, studies are underway to differentiate ESCs in to tissue specific CMs and to eradicate their immature properties that distinguish them from adult CMs.[10]

Besides becoming an important alternative to organ transplants, ESCs are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ESCs are validated in vitro models to test drug responses and predict toxicity profiles.[9] ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes.[17]

ESC-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery. However, the development of hepatocytes from ESCs has proven to be challenging and this hinders the ability to test drug metabolism. Therefore, current research is focusing on establishing fully functional ESC-derived hepatocytes with stable phase I and II enzyme activity.[18]

Several new studies have started to address the concept of modeling genetic disorders with embryonic stem cells. Either by genetically manipulating the cells, or more recently, by deriving diseased cell lines identified by prenatal genetic diagnosis (PGD), modeling genetic disorders is something that has been accomplished with stem cells. This approach may very well prove invaluable at studying disorders such as Fragile-X syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model system.

Yury Verlinsky, a Russian-American medical researcher who specialized in embryo and cellular genetics (genetic cytology), developed prenatal diagnosis testing methods to determine genetic and chromosomal disorders a month and a half earlier than standard amniocentesis. The techniques are now used by many pregnant women and prospective parents, especially couples who have a history of genetic abnormalities or where the woman is over the age of 35 (when the risk of genetically related disorders is higher). In addition, by allowing parents to select an embryo without genetic disorders, they have the potential of saving the lives of siblings that already had similar disorders and diseases using cells from the disease free offspring.[19]

Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage. For instance, human foreskin fibroblasts, one type of somatic cell, use non-homologous end joining (NHEJ), an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.[20] Because of its error-prone nature, NHEJ tends to produce mutations in a cells clonal descendants.

ES cells use a different strategy to deal with DSBs.[21] Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently, robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages. Thus, mouse ES cells predominantly use high fidelity homologous recombinational repair (HRR) to repair DSBs.[21] This type of repair depends on the interaction of the two sister chromosomes formed during S phase and present together during the G2 phase of the cell cycle. HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome. Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes arent present). Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage.[22] Rather they undergo programmed cell death (apoptosis) in response to DNA damage.[23] Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer.[24] Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells.[25]

On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world's first human ES cell human trial.[26] The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage.[27] The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities.[28] The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010.[29]

In October 2010 researchers enrolled and administered ESTs to the first patient at Shepherd Center in Atlanta.[30] The makers of the stem cell therapy, Geron Corporation, estimated that it would take several months for the stem cells to replicate and for the GRNOPC1 therapy to be evaluated for success or failure.

In November 2011 Geron announced it was halting the trial and dropping out of stem cell research for financial reasons, but would continue to monitor existing patients, and was attempting to find a partner that could continue their research.[31] In 2013 BioTime (AMEX:BTX), led by CEO Dr. Michael D. West, acquired all of Geron's stem cell assets, with the stated intention of restarting Geron's embryonic stem cell-based clinical trial for spinal cord injury research.[32]

BioTime company Asterias Biotherapeutics (NYSE MKT: AST) was granted a $14.3 million Strategic Partnership Award by the California Institute for Regenerative Medicine (CIRM) to re-initiate the worlds first embryonic stem cell-based human clinical trial, for spinal cord injury. Supported by California public funds, CIRM is the largest funder of stem cell-related research and development in the world.[33]

The award provides funding for Asterias to reinitiate clinical development of AST-OPC1 in subjects with spinal cord injury and to expand clinical testing of escalating doses in the target population intended for future pivotal trials.[33]

AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and their mature derivatives called oligodendrocytes provide critical functional support for nerve cells in the spinal cord and brain. Asterias recently presented the results from phase 1 clinical trial testing of a low dose of AST-OPC1 in patients with neurologically-complete thoracic spinal cord injury. The results showed that AST-OPC1 was successfully delivered to the injured spinal cord site. Patients followed 23 years after AST-OPC1 administration showed no evidence of serious adverse events associated with the cells in detailed follow-up assessments including frequent neurological exams and MRIs. Immune monitoring of subjects through one year post-transplantation showed no evidence of antibody-based or cellular immune responses to AST-OPC1. In four of the five subjects, serial MRI scans performed throughout the 23 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration. There was no unexpected neurological degeneration or improvement in the five subjects in the trial as evaluated by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam.[33]

The Strategic Partnership III grant from CIRM will provide funding to Asterias to support the next clinical trial of AST-OPC1 in subjects with spinal cord injury, and for Asterias product development efforts to refine and scale manufacturing methods to support later-stage trials and eventually commercialization. CIRM funding will be conditional on FDA approval for the trial, completion of a definitive agreement between Asterias and CIRM, and Asterias continued progress toward the achievement of certain pre-defined project milestones.[33]

The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma.[34] Safety issues prompted the FDA to place a hold on the first ESC clinical trial, however no tumors were observed.

The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells created with genetically-integrating viral vectors because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency,[35] and potential strategies to improve safety by eliminating c-Myc expression are unlikely to preserve the cells' "stemness". However, N-myc and L-myc have been identified to induce iPS cells instead of c-myc with similar efficiency.[36]More recent protocols to induce pluripotency bypass these problems completely by using non-integrating RNA viral vectors such as sendai virus or mRNA transfection.

Due to the nature of embryonic stem cell research, there is a lot of controversial opinions on the topic. Since harvesting embryonic stem cells necessitates destroying the embryo from which those cells are obtained, the moral status of the embryo comes into question. Scientists argue that the 5-day old mass of cells is too young to achieve personhood or that the embryo, if donated from an IVF clinic (which is where labs typically acquire embryos from), would otherwise go to medical waste anyway. Opponents of ESC research counter that any embryo has the potential to become a human, therefore destroying it is murder and the embryo must be protected under the same ethical view as a developed human being.[37]

In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg.[49] The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result.[50]

Embryonic stem cells are derived from the inner cell mass of the early embryo, which are harvested from the donor mother animal. Martin Evans and Matthew Kaufman reported a technique that delays embryo implantation, allowing the inner cell mass to increase. This process includes removing the donor mother's ovaries and dosing her with progesterone, changing the hormone environment, which causes the embryos to remain free in the uterus. After 46 days of this intrauterine culture, the embryos are harvested and grown in in vitro culture until the inner cell mass forms egg cylinder-like structures, which are dissociated into single cells, and plated on fibroblasts treated with mitomycin-c (to prevent fibroblast mitosis). Clonal cell lines are created by growing up a single cell. Evans and Kaufman showed that the cells grown out from these cultures could form teratomas and embryoid bodies, and differentiate in vitro, all of which indicating that the cells are pluripotent.[41]

Gail Martin derived and cultured her ES cells differently. She removed the embryos from the donor mother at approximately 76 hours after copulation and cultured them overnight in a medium containing serum. The following day, she removed the inner cell mass from the late blastocyst using microsurgery. The extracted inner cell mass was cultured on fibroblasts treated with mitomycin-c in a medium containing serum and conditioned by ES cells. After approximately one week, colonies of cells grew out. These cells grew in culture and demonstrated pluripotent characteristics, as demonstrated by the ability to form teratomas, differentiate in vitro, and form embryoid bodies. Martin referred to these cells as ES cells.[42]

It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating.[51][52] These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells.[53] Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells).[54]

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo.[55] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted.[56]

The iPSC technology was pioneered by Shinya Yamanakas lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells.[57] He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." [58]

In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells.[59] The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.[60]

This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases.

However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online edition on December 6, 2007.[61][62]

On January 16, 2008, a California-based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells.[63]

The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[64] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[65]

However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines.[66]

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Stem cell, an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. There is great interest in stem cells because they have potential in the development of therapies for replacing defective or damaged cells resulting from a variety of disorders and injuries, such as Parkinson disease, heart disease, and diabetes. There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells.

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cardiovascular disease: Cardiac stem cells

Cardiac stem cells, which have the ability to differentiate (specialize) into mature heart cells and therefore could be used to repair damaged or diseased heart tissue, have garnered significant interest in the development of treatments for heart disease and cardiac defects. Cardiac stem

Embryonic stem cells (often referred to as ES cells) are stem cells that are derived from the inner cell mass of a mammalian embryo at a very early stage of development, when it is composed of a hollow sphere of dividing cells (a blastocyst). Embryonic stem cells from human embryos and from embryos of certain other mammalian species can be grown in tissue culture.

The most-studied embryonic stem cells are mouse embryonic stem cells, which were first reported in 1981. This type of stem cell can be cultured indefinitely in the presence of leukemia inhibitory factor (LIF), a glycoprotein cytokine. If cultured mouse embryonic stem cells are injected into an early mouse embryo at the blastocyst stage, they will become integrated into the embryo and produce cells that differentiate into most or all of the tissue types that subsequently develop. This ability to repopulate mouse embryos is the key defining feature of embryonic stem cells, and because of it they are considered to be pluripotentthat is, able to give rise to any cell type of the adult organism. If the embryonic stem cells are kept in culture in the absence of LIF, they will differentiate into embryoid bodies, which somewhat resemble early mouse embryos at the egg-cylinder stage, with embryonic stem cells inside an outer layer of endoderm. If embryonic stem cells are grafted into an adult mouse, they will develop into a type of tumour called a teratoma, which contains a variety of differentiated tissue types.

Mouse embryonic stem cells are widely used to create genetically modified mice. This is done by introducing new genes into embryonic stem cells in tissue culture, selecting the particular genetic variant that is desired, and then inserting the genetically modified cells into mouse embryos. The resulting chimeric mice are composed partly of host cells and partly of the donor embryonic stem cells. As long as some of the chimeric mice have germ cells (sperm or eggs) that have been derived from the embryonic stem cells, it is possible to breed a line of mice that have the same genetic constitution as the embryonic stem cells and therefore incorporate the genetic modification that was made in vitro. This method has been used to produce thousands of new genetic lines of mice. In many such genetic lines, individual genes have been ablated in order to study their biological function; in others, genes have been introduced that have the same mutations that are found in various human genetic diseases. These mouse models for human disease are used in research to investigate both the pathology of the disease and new methods for therapy.

Extensive experience with mouse embryonic stem cells made it possible for scientists to grow human embryonic stem cells from early human embryos, and the first human stem cell line was created in 1998. Human embryonic stem cells are in many respects similar to mouse embryonic stem cells, but they do not require LIF for their maintenance. The human embryonic stem cells form a wide variety of differentiated tissues in vitro, and they form teratomas when grafted into immunosuppressed mice. It is not known whether the cells can colonize all the tissues of a human embryo, but it is presumed from their other properties that they are indeed pluripotent cells, and they therefore are regarded as a possible source of differentiated cells for cell therapythe replacement of a patients defective cell type with healthy cells. Large quantities of cells, such as dopamine-secreting neurons for the treatment of Parkinson disease and insulin-secreting pancreatic beta cells for the treatment of diabetes, could be produced from embryonic stem cells for cell transplantation. Cells for this purpose have previously been obtainable only from sources in very limited supply, such as the pancreatic beta cells obtained from the cadavers of human organ donors.

The use of human embryonic stem cells evokes ethical concerns, because the blastocyst-stage embryos are destroyed in the process of obtaining the stem cells. The embryos from which stem cells have been obtained are produced through in vitro fertilization, and people who consider preimplantation human embryos to be human beings generally believe that such work is morally wrong. Others accept it because they regard the blastocysts to be simply balls of cells, and human cells used in laboratories have not previously been accorded any special moral or legal status. Moreover, it is known that none of the cells of the inner cell mass are exclusively destined to become part of the embryo itselfall of the cells contribute some or all of their cell offspring to the placenta, which also has not been accorded any special legal status. The divergence of views on this issue is illustrated by the fact that the use of human embryonic stem cells is allowed in some countries and prohibited in others.

In 2009 the U.S. Food and Drug Administration approved the first clinical trial designed to test a human embryonic stem cell-based therapy, but the trial was halted in late 2011 because of a lack of funding and a change in lead American biotech company Gerons business directives. The therapy to be tested was known as GRNOPC1, which consisted of progenitor cells (partially differentiated cells) that, once inside the body, matured into neural cells known as oligodendrocytes. The oligodendrocyte progenitors of GRNOPC1 were derived from human embryonic stem cells. The therapy was designed for the restoration of nerve function in persons suffering from acute spinal cord injury.

Embryonic germ (EG) cells, derived from primordial germ cells found in the gonadal ridge of a late embryo, have many of the properties of embryonic stem cells. The primordial germ cells in an embryo develop into stem cells that in an adult generate the reproductive gametes (sperm or eggs). In mice and humans it is possible to grow embryonic germ cells in tissue culture with the appropriate growth factorsnamely, LIF and another cytokine called fibroblast growth factor.

Some tissues in the adult body, such as the epidermis of the skin, the lining of the small intestine, and bone marrow, undergo continuous cellular turnover. They contain stem cells, which persist indefinitely, and a much larger number of transit amplifying cells, which arise from the stem cells and divide a finite number of times until they become differentiated. The stem cells exist in niches formed by other cells, which secrete substances that keep the stem cells alive and active. Some types of tissue, such as liver tissue, show minimal cell division or undergo cell division only when injured. In such tissues there is probably no special stem-cell population, and any cell can participate in tissue regeneration when required.

The epidermis of the skin contains layers of cells called keratinocytes. Only the basal layer, next to the dermis, contains cells that divide. A number of these cells are stem cells, but the majority are transit amplifying cells. The keratinocytes slowly move outward through the epidermis as they mature, and they eventually die and are sloughed off at the surface of the skin. The epithelium of the small intestine forms projections called villi, which are interspersed with small pits called crypts. The dividing cells are located in the crypts, with the stem cells lying near the base of each crypt. Cells are continuously produced in the crypts, migrate onto the villi, and are eventually shed into the lumen of the intestine. As they migrate, they differentiate into the cell types characteristic of the intestinal epithelium.

Bone marrow contains cells called hematopoietic stem cells, which generate all the cell types of the blood and the immune system. Hematopoietic stem cells are also found in small numbers in peripheral blood and in larger numbers in umbilical cord blood. In bone marrow, hematopoietic stem cells are anchored to osteoblasts of the trabecular bone and to blood vessels. They generate progeny that can become lymphocytes, granulocytes, red blood cells, and certain other cell types, depending on the balance of growth factors in their immediate environment.

Work with experimental animals has shown that transplants of hematopoietic stem cells can occasionally colonize other tissues, with the transplanted cells becoming neurons, muscle cells, or epithelia. The degree to which transplanted hematopoietic stem cells are able to colonize other tissues is exceedingly small. Despite this, the use of hematopoietic stem cell transplants is being explored for conditions such as heart disease or autoimmune disorders. It is an especially attractive option for those opposed to the use of embryonic stem cells.

Bone marrow transplants (also known as bone marrow grafts) represent a type of stem cell therapy that is in common use. They are used to allow cancer patients to survive otherwise lethal doses of radiation therapy or chemotherapy that destroy the stem cells in bone marrow. For this procedure, the patients own marrow is harvested before the cancer treatment and is then reinfused into the body after treatment. The hematopoietic stem cells of the transplant colonize the damaged marrow and eventually repopulate the blood and the immune system with functional cells. Bone marrow transplants are also often carried out between individuals (allograft). In this case the grafted marrow has some beneficial antitumour effect. Risks associated with bone marrow allografts include rejection of the graft by the patients immune system and reaction of immune cells of the graft against the patients tissues (graft-versus-host disease).

Bone marrow is a source for mesenchymal stem cells (sometimes called marrow stromal cells, or MSCs), which are precursors to non-hematopoietic stem cells that have the potential to differentiate into several different types of cells, including cells that form bone, muscle, and connective tissue. In cell cultures, bone-marrow-derived mesenchymal stem cells demonstrate pluripotency when exposed to substances that influence cell differentiation. Harnessing these pluripotent properties has become highly valuable in the generation of transplantable tissues and organs. In 2008 scientists used mesenchymal stem cells to bioengineer a section of trachea that was transplanted into a woman whose upper airway had been severely damaged by tuberculosis. The stem cells were derived from the womans bone marrow, cultured in a laboratory, and used for tissue engineering. In the engineering process, a donor trachea was stripped of its interior and exterior cell linings, leaving behind a trachea scaffold of connective tissue. The stem cells derived from the recipient were then used to recolonize the interior of the scaffold, and normal epithelial cells, also isolated from the recipient, were used to recolonize the exterior of the trachea. The use of the recipients own cells to populate the trachea scaffold prevented immune rejection and eliminated the need for immunosuppression therapy. The transplant, which was successful, was the first of its kind.

Research has shown that there are also stem cells in the brain. In mammals very few new neurons are formed after birth, but some neurons in the olfactory bulbs and in the hippocampus are continually being formed. These neurons arise from neural stem cells, which can be cultured in vitro in the form of neurospheressmall cell clusters that contain stem cells and some of their progeny. This type of stem cell is being studied for use in cell therapy to treat Parkinson disease and other forms of neurodegeneration or traumatic damage to the central nervous system.

Following experiments in animals, including those used to create Dolly the sheep, there has been much discussion about the use of somatic cell nuclear transfer (SCNT) to create pluripotent human cells. In SCNT the nucleus of a somatic cell (a fully differentiated cell, excluding germ cells), which contains the majority of the cells DNA (deoxyribonucleic acid), is removed and transferred into an unfertilized egg cell that has had its own nuclear DNA removed. The egg cell is grown in culture until it reaches the blastocyst stage. The inner cell mass is then removed from the egg, and the cells are grown in culture to form an embryonic stem cell line (generations of cells originating from the same group of parent cells). These cells can then be stimulated to differentiate into various types of cells needed for transplantation. Since these cells would be genetically identical to the original donor, they could be used to treat the donor with no problems of immune rejection. Scientists generated human embryonic stem cells successfully from SCNT human embryos for the first time in 2013.

While promising, the generation and use of SCNT-derived embryonic stem cells is controversial for several reasons. One is that SCNT can require more than a dozen eggs before one egg successfully produces embryonic stem cells. Human eggs are in short supply, and there are many legal and ethical problems associated with egg donation. There are also unknown risks involved with transplanting SCNT-derived stem cells into humans, because the mechanism by which the unfertilized egg is able to reprogram the nuclear DNA of a differentiated cell is not entirely understood. In addition, SCNT is commonly used to produce clones of animals (such as Dolly). Although the cloning of humans is currently illegal throughout the world, the egg cell that contains nuclear DNA from an adult cell could in theory be implanted into a womans uterus and come to term as an actual cloned human. Thus, there exists strong opposition among some groups to the use of SCNT to generate human embryonic stem cells.

Due to the ethical and moral issues surrounding the use of embryonic stem cells, scientists have searched for ways to reprogram adult somatic cells. Studies of cell fusion, in which differentiated adult somatic cells grown in culture with embryonic stem cells fuse with the stem cells and acquire embryonic stem-cell-like properties, led to the idea that specific genes could reprogram differentiated adult cells. An advantage of cell fusion is that it relies on existing embryonic stem cells instead of eggs. However, fused cells stimulate an immune response when transplanted into humans, which leads to transplant rejection. As a result, research has become increasingly focused on the genes and proteins capable of reprogramming adult cells to a pluripotent state. In order to make adult cells pluripotent without fusing them to embryonic stem cells, regulatory genes that induce pluripotency must be introduced into the nuclei of adult cells. To do this, adult cells are grown in cell culture, and specific combinations of regulatory genes are inserted into retroviruses (viruses that convert RNA [ribonucleic acid] into DNA), which are then introduced to the culture medium. The retroviruses transport the RNA of the regulatory genes into the nuclei of the adult cells, where the genes are then incorporated into the DNA of the cells. About 1 out of every 10,000 cells acquires embryonic stem cell properties. Although the mechanism is still uncertain, it is clear that some of the genes confer embryonic stem cell properties by means of the regulation of numerous other genes. Adult cells that become reprogrammed in this way are known as induced pluripotent stem cells (iPS).

Similar to embryonic stem cells, induced pluripotent stem cells can be stimulated to differentiate into select types of cells that could in principle be used for disease-specific treatments. In addition, the generation of induced pluripotent stem cells from the adult cells of patients affected by genetic diseases can be used to model the diseases in the laboratory. For example, in 2008 researchers isolated skin cells from a child with an inherited neurological disease called spinal muscular atrophy and then reprogrammed these cells into induced pluripotent stem cells. The reprogrammed cells retained the disease genotype of the adult cells and were stimulated to differentiate into motor neurons that displayed functional insufficiencies associated with spinal muscular atrophy. By recapitulating the disease in the laboratory, scientists were able to study closely the cellular changes that occurred as the disease progressed. Such models promise not only to improve scientists understanding of genetic diseases but also to facilitate the development of new therapeutic strategies tailored to each type of genetic disease.

In 2009 scientists successfully generated retinal cells of the human eye by reprogramming adult skin cells. This advance enabled detailed investigation of the embryonic development of retinal cells and opened avenues for the generation of novel therapies for eye diseases. The production of retinal cells from reprogrammed skin cells may be particularly useful in the treatment of retinitis pigmentosa, which is characterized by the progressive degeneration of the retina, eventually leading to night blindness and other complications of vision. Although retinal cells also have been produced from human embryonic stem cells, induced pluripotency represents a less controversial approach. Scientists have also explored the possibility of combining induced pluripotent stem cell technology with gene therapy, which would be of value particularly for patients with genetic disease who would benefit from autologous transplantation.

Researchers have also been able to generate cardiac stem cells for the treatment of certain forms of heart disease through the process of dedifferentiation, in which mature heart cells are stimulated to revert to stem cells. The first attempt at the transplantation of autologous cardiac stem cells was performed in 2009, when doctors isolated heart tissue from a patient, cultured the tissue in a laboratory, stimulated cell dedifferentiation, and then reinfused the cardiac stem cells directly into the patients heart. A similar study involving 14 patients who underwent cardiac bypass surgery followed by cardiac stem cell transplantation was reported in 2011. More than three months after stem cell transplantation, the patients experienced a slight but detectable improvement in heart function.

Patient-specific induced pluripotent stem cells and dedifferentiated cells are highly valuable in terms of their therapeutic applications because they are unlikely to be rejected by the immune system. However, before induced pluripotent stem cells can be used to treat human diseases, researchers must find a way to introduce the active reprogramming genes without using retroviruses, which can cause diseases such as leukemia in humans. A possible alternative to the use of retroviruses to transport regulatory genes into the nuclei of adult cells is the use of plasmids, which are less tumourigenic than viruses.

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Stem cell facts

What are stem cells?

Stem cells are cells that have the potential to develop into many different or specialized cell types. Stem cells can be thought of as primitive, "unspecialized" cells that are able to divide and become specialized cells of the body such as liver cells, muscle cells, blood cells, and other cells with specific functions. Stem cells are referred to as "undifferentiated" cells because they have not yet committed to a developmental path that will form a specific tissue or organ. The process of changing into a specific cell type is known as differentiation. In some areas of the body, stem cells divide regularly to renew and repair the existing tissue. The bone marrow and gastrointestinal tract are examples of areas in which stem cells function to renew and repair tissue.

The best and most readily understood example of a stem cell in humans is that of the fertilized egg, or zygote. A zygote is a single cell that is formed by the union of a sperm and ovum. The sperm and the ovum each carry half of the genetic material required to form a new individual. Once that single cell or zygote starts dividing, it is known as an embryo. One cell becomes two, two become four, four become eight, eight become sixteen, and so on, doubling rapidly until it ultimately grows into an entire sophisticated organism composed of many different kinds of specialized cells. That organism, a person, is an immensely complicated structure consisting of many, many, billions of cells with functions as diverse as those of your eyes, your heart, your immune system, the color of your skin, your brain, etc. All of the specialized cells that make up these body systems are descendants of the original zygote, a stem cell with the potential to ultimately develop into all kinds of body cells. The cells of a zygote are totipotent, meaning that they have the capacity to develop into any type of cell in the body.

The process by which stem cells commit to become differentiated, or specialized, cells is complex and involves the regulation of gene expression. Research is ongoing to further understand the molecular events and controls necessary for stem cells to become specialized cell types.

Stem Cells:One of the human body's master cells, with the ability to grow into any one of the body's more than 200 cell types.

All stem cells are unspecialized (undifferentiated) cells that are characteristically of the same family type (lineage). They retain the ability to divide throughout life and give rise to cells that can become highly specialized and take the place of cells that die or are lost.

Stem cells contribute to the body's ability to renew and repair its tissues. Unlike mature cells, which are permanently committed to their fate, stem cells can both renew themselves as well as create new cells of whatever tissue they belong to (and other tissues).

Why are stem cells important?

Stem cells represent an exciting area in medicine because of their potential to regenerate and repair damaged tissue. Some current therapies, such as bone marrow transplantation, already make use of stem cells and their potential for regeneration of damaged tissues. Other therapies that are under investigation involve transplanting stem cells into a damaged body part and directing them to grow and differentiate into healthy tissue.

Embryonic stem cells

During the early stages of embryonic development the cells remain relatively undifferentiated (immature) and appear to possess the ability to become, or differentiate, into almost any tissue within the body. For example, cells taken from one section of an embryo that might have become part of the eye can be transferred into another section of the embryo and could develop into blood, muscle, nerve, or liver cells.

Cells in the early embryonic stage are totipotent (see above) and can differentiate to become any type of body cell. After about seven days, the zygote forms a structure known as a blastocyst, which contains a mass of cells that eventually become the fetus, as well as trophoblastic tissue that eventually becomes the placenta. If cells are taken from the blastocyst at this stage, they are known as pluripotent, meaning that they have the capacity to become many different types of human cells. Cells at this stage are often referred to as blastocyst embryonic stem cells. When any type of embryonic stem cells is grown in culture in the laboratory, they can divide and grow indefinitely. These cells are then known as embryonic stem cell lines.

Fetal stem cells

The embryo is referred to as a fetus after the eighth week of development. The fetus contains stem cells that are pluripotent and eventually develop into the different body tissues in the fetus.

Adult stem cells

Adult stem cells are present in all humans in small numbers. The adult stem cell is one of the class of cells that we have been able to manipulate quite effectively in the bone marrow transplant arena over the past 30 years. These are stem cells that are largely tissue-specific in their location. Rather than typically giving rise to all of the cells of the body, these cells are capable of giving rise only to a few types of cells that develop into a specific tissue or organ. They are therefore known as multipotent stem cells. Adult stem cells are sometimes referred to as somatic stem cells.

The best characterized example of an adult stem cell is the blood stem cell (the hematopoietic stem cell). When we refer to a bone marrow transplant, a stem cell transplant, or a blood transplant, the cell being transplanted is the hematopoietic stem cell, or blood stem cell. This cell is a very rare cell that is found primarily within the bone marrow of the adult.

One of the exciting discoveries of the last years has been the overturning of a long-held scientific belief that an adult stem cell was a completely committed stem cell. It was previously believed that a hematopoietic, or blood-forming stem cell, could only create other blood cells and could never become another type of stem cell. There is now evidence that some of these apparently committed adult stem cells are able to change direction to become a stem cell in a different organ. For example, there are some models of bone marrow transplantation in rats with damaged livers in which the liver partially re-grows with cells that are derived from transplanted bone marrow. Similar studies can be done showing that many different cell types can be derived from each other. It appears that heart cells can be grown from bone marrow stem cells, that bone marrow cells can be grown from stem cells derived from muscle, and that brain stem cells can turn into many types of cells.

Peripheral blood stem cells

Most blood stem cells are present in the bone marrow, but a few are present in the bloodstream. This means that these so-called peripheral blood stem cells (PBSCs) can be isolated from a drawn blood sample. The blood stem cell is capable of giving rise to a very large number of very different cells that make up the blood and immune system, including red blood cells, platelets, granulocytes, and lymphocytes.

All of these very different cells with very different functions are derived from a common, ancestral, committed blood-forming (hematopoietic), stem cell.

Umbilical cord stem cells

Blood from the umbilical cord contains some stem cells that are genetically identical to the newborn. Like adult stem cells, these are multipotent stem cells that are able to differentiate into certain, but not all, cell types. For this reason, umbilical cord blood is often banked, or stored, for possible future use should the individual require stem cell therapy.

Induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) were first created from human cells in 2007. These are adult cells that have been genetically converted to an embryonic stem celllike state. In animal studies, iPSCs have been shown to possess characteristics of pluripotent stem cells. Human iPSCs can differentiate and become multiple different fetal cell types. iPSCs are valuable aids in the study of disease development and drug treatment, and they may have future uses in transplantation medicine. Further research is needed regarding the development and use of these cells.

Why is there controversy surrounding the use of stem cells?

Embryonic stem cells and embryonic stem cell lines have received much public attention concerning the ethics of their use or non-use. Clearly, there is hope that a large number of treatment advances could occur as a result of growing and differentiating these embryonic stem cells in the laboratory. It is equally clear that each embryonic stem cell line has been derived from a human embryo created through in-vitro fertilization (IVF) or through cloning technologies, with all the attendant ethical, religious, and philosophical problems, depending upon one's perspective.

What are some stem cell therapies that are currently available?

Routine use of stem cells in therapy has been limited to blood-forming stem cells (hematopoietic stem cells) derived from bone marrow, peripheral blood, or umbilical cord blood. Bone marrow transplantation is the most familiar form of stem cell therapy and the only instance of stem cell therapy in common use. It is used to treat cancers of the blood cells (leukemias) and other disorders of the blood and bone marrow.

In bone marrow transplantation, the patient's existing white blood cells and bone marrow are destroyed using chemotherapy and radiation therapy. Then, a sample of bone marrow (containing stem cells) from a healthy, immunologically matched donor is injected into the patient. The transplanted stem cells populate the recipient's bone marrow and begin producing new, healthy blood cells.

Umbilical cord blood stem cells and peripheral blood stem cells can also be used instead of bone marrow samples to repopulate the bone marrow in the process of bone marrow transplantation.

In 2009, the California-based company Geron received clearance from the U. S. Food and Drug Administration (FDA) to begin the first human clinical trial of cells derived from human embryonic stem cells in the treatment of patients with acute spinal cord injury.

What are experimental treatments using stem cells and possible future directions for stem cell therapy?

Stem cell therapy is an exciting and active field of biomedical research. Scientists and physicians are investigating the use of stem cells in therapies to treat a wide variety of diseases and injuries. For a stem cell therapy to be successful, a number of factors must be considered. The appropriate type of stem cell must be chosen, and the stem cells must be matched to the recipient so that they are not destroyed by the recipient's immune system. It is also critical to develop a system for effective delivery of the stem cells to the desired location in the body. Finally, devising methods to "switch on" and control the differentiation of stem cells and ensure that they develop into the desired tissue type is critical for the success of any stem cell therapy.

Researchers are currently examining the use of stem cells to regenerate damaged or diseased tissue in many conditions, including those listed below.

References

REFERENCE:

"Stem Cell Information." National Institutes of Health.

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Skin Stem Cells Comments Off on Stem Cells – MedicineNet | September 16th, 2018

Stem cells are a huge trend in skincare, but what do they really do for your skin? Stem cells are often called blank cells because they are undifferentiated, meaning they can be duplicated and made into any type of cell. Think of stem cells as blank scrabble pieces, they can fill in where there are needed because they have the ability to turn into specialized cells. They can boost collagen, protect against sun damage, brighten and repair damaged cells.

PCA SKIN uses plant stem cell extracts from oranges, lilac and grapes as ingredients in several products. All plant stem cells provide antioxidant protection, adding an extra boost of skin-health benefits to an established regimen. Specifically, they guard against inflammation, neutralize free radicals and reverse sun damage. Plant stem cell extracts, versus the actual stem cell, are used in skincare because they are the purest, most-stable way of ensuring the quality of the ingredient. While the actual stem cell cant survive outside of the plant, the extract is just as effective.

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Cardiac stem cell research has a turbulent history. Studies revealing the presence of regenerative progenitors in adult rodents hearts formed the basis of numerous clinical trials, but several experiments have cast doubt on these cells ability to produce new tissue. Some scientists are now lauding the results of a report published in April in Circulation as undeniable evidence against the idea that resident stem cells can give rise to new cardiomyocytes.

The concept of [many] clinical trials arose from the basic science in labs of a few individuals more than 15 years ago, and that basic science is whats now being called into question, says Jeffery Molkentin, a cardiovascular biologist at Cincinnati Childrens Hospital who penned an editorial about the latest work.

The first evidence supporting the notion of cardiac stem cells in adults emerged in the early 2000s, when researchers reported that cells derived from bone marrow or adult heart expressing the protein c-kit could give rise to new muscle tissue when injected into damaged myocardium in rodents. These studies caused some controversy right from the start, Molkentin says. The main reason that this struck a raw nerve with people is because we already know that heart, in human patients, doesnt regenerate itself after an infarct.

Early skepticism arose in 2004, when two separate groups of researchers published back-to-back papers refuting the claims that bone marrowderived c-kit cells could regenerate damaged heart tissue. Still, the concept of endogenous cardiac stem cells remained a mainstream idea until Molkentin and his colleagues published a study in 2014 reporting that c-kit cells in the adult mouse heart almost never produced new cardiomyocytes, says Bin Zhou, a cell biologist at the Chinese Academy of Sciences and a coauthor of the new study.

Although Molkentins findings were replicated shortly afterwards by two independent groups (including Zhous), some researchers held fast to the idea that cardiac progenitors could regenerate injured heart tissue. Earlier this year, a team of researchersincluding Bernardo Nadal-Ginard and Daniele Torella of Magna Graecia University in Italy and several other scientists who conducted the early work on c-kit cellspublished a paper reporting the flaws in the cell lineage tracing technique employed by Molkentin, Zhou, and their colleagues. For example, they noted that the method, which involved tagging c-kitexpressing cells and their progeny with a fluorescent marker, compromised the gene required to express the c-kit protein, impairing the progenitors regenerative abilities.

In the new Circulationstudy, Zhou and his colleagues used a different approach to examine endogenous stem cell populations in mice. Instead of tagging c-kit cells, the team applied a technique that would fluorescently label nonmyocytes and newly generated muscle cells a different color from existing myocytes. This method allowed the researchers to investigate all proposed stem cell populations, rather than specifically addressing c-kit cells. We wanted to ask the broader question of whether there are any stem cells in the adult heart, Zhou says.

These experiments revealed that, while nonmyocytes generate cardiomyocytes in mouse embryos, they do not give rise to new muscle cells in adult rodents hearts. The results also address the concerns raised about c-kit lineage tracing, Zhou tells The Scientist. We think our system can conclude that nonmyocytes cannot become myocytes in adults in homeostasis and after injury.

Torella says that hes not convinced by Zhous evidence. The main issue, he explains, is that the researchers did not explicitly test whether cardiac stem cells were indeed labeled as nonmyocytes to ensure that they were not inadvertently tagging them as myocytes instead.

Molkentin disagrees with this critique, stating that the only way the system would label a myocyte progenitor as a myocyte is if it was no longer a true stem cell, but instead an immature myocyte. Zhous group uses an exhausting and very rigorous genetic approach, he adds. My opinion is that we need to go back to the bench and conduct additional research to truly understand the mechanisms at play to better inform how we design the next generation of clinical trials.

Other scientists note that stem cells may not need to become new myocytes to help repair the injured heart. According to Phillip Yang, a cardiologist at Stanford University who did not take part in the work, many scientists now agree that stem cells are not regenerating damaged cardiomyocytes. Instead, he explains, a growing body of research now supports an alternative theory, which posits that progenitor cells secrete small molecules called paracrine factors that help repair injured heart cells. (Yang is involved in several stem cell clinical trials).

When you inject these stem cells, its pretty incontrovertible that they help heart function in a mouse injury model, Yang says. But the truth is, most of these cells are dead upon arrival [to the site of injury]. So the question is: Why is heart function still improving if these cells are dying?

Y. Li et al., Genetic lineage tracing of nonmyocyte population by dual recombinases, Circulation, 138:793-805, 2018.

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According to the National Spinal Cord Injury Association, as many as 450,000 people in the U.S. are living with a spinal cord injury (SCI). Other organizations conservatively estimate this figure to be about 250,000.

The spinal cord is about 18 inches long, extending from the base of the brain to near the waist. Many of the bundles of nerve fibers that make up the spinal cord itself contain upper motor neurons (UMNs). Spinal nerves that branch off the spinal cord at regular intervals in the neck and back contain lower motor neurons (LMNs).

Types and Levels of SCI

The severity of an injury depends on the part of the spinal cord that is affected. The higher the SCI on the vertebral column, or the closer it is to the brain, the more effect it has on how the body moves and what one can feel. More movement, feeling and voluntary control are generally present with injuries at lower levels.

Tetraplegia (a.k.a. quadriplegia) results from injuries to the spinal cord in the cervical (neck) region, with associated loss of muscle strength in all four extremities.

Paraplegia results from injuries to the spinal cord in the thoracic or lumbar areas, resulting in paralysis of the legs and lower part of the body.

Complete SCI

A complete SCI produces total loss of all motor and sensory function below the level of injury. Nearly 50 percent of all SCIs are complete. Both sides of the body are equally affected. Even with a complete SCI, the spinal cord is rarely cut or transected. More commonly, loss of function is caused by a contusion or bruise to the spinal cord or by compromise of blood flow to the injured part of the spinal cord.

Incomplete SCI

In an incomplete SCI, some function remains below the primary level of the injury. A person with an incomplete injury may be able to move one arm or leg more than the other or may have more functioning on one side of the body than the other. An incomplete SCI often falls into one of several patterns.

Anterior cord syndrome results from injury to the motor and sensory pathways in the anterior parts of the spinal cord. These patients can feel some types of crude sensation via the intact pathways in the posterior part of the spinal cord, but movement and more detailed sensation are lost.

Central cord syndrome usually results from trauma and is associated with damage to the large nerve fibers that carry information directly from the cerebral cortex to the spinal cord. Symptoms may include paralysis and/or loss of fine control of movements in the arms and hands, with far less impairment of leg movements. Sensory loss below the site of the SCI and loss of bladder control may also occur, with the overall amount and type of functional loss related to the severity of damage to the nerves of the spinal cord.

Brown-Sequard syndrome is a rare spinal disorder that results from an injury to one side of the spinal cord. It is usually caused by an injury to the spine in the region of the neck or back. In many cases, some type of puncture wound in the neck or in the back that damages the spine may be the cause. Movement and some types of sensation are lost below the level of injury on the injured side. Pain and temperature sensation are lost on the side of the body opposite the injury because these pathways cross to the opposite side shortly after they enter the spinal cord.

Injuries to a specific nerve root may occur either by themselves or together with a SCI. Because each nerve root supplies motor and sensory function to a different part of the body, the symptoms produced by this injury depend upon the pattern of distribution of the specific nerve root involved.

"Spinal concussions" can also occur. These can be complete or incomplete, but spinal cord dysfunction is transient, generally resolving within one or two days. Football players are especially susceptible to spinal concussions and spinal cord contusions. The latter may produce neurological symptoms including numbness, tingling, electric shock-like sensations and burning in the extremities. Fracture-dislocations with ligamentous tears may be present in this syndrome.

Penetrating SCI

"Open" or penetrating injuries to the spine and spinal cord, especially those caused by firearms, may present somewhat different challenges. Most gunshot wounds to the spine are stable; i.e., they do not carry as much risk of excessive and potentially dangerous motion of the injured parts of the spine. Depending upon the anatomy of the injury, the patient may need to be immobilized with a collar or brace for several weeks or months so that the parts of the spine that were fractured by the bullet may heal. In most cases, surgery to remove the bullet does not yield much benefit and may create additional risks, including infection, cerebrospinal fluid leak and bleeding. However, occasional cases of gunshot wounds to the spine may require surgical decompression and/or fusion in an attempt to optimize patient outcome.

Diagnosis

When SCI is suspected, immediate medical attention is required. SCI is usually first diagnosed when the patient presents with loss of function below the level of injury.

Signs and Symptoms of Possible SCI:

Clinical Evaluation

A physician may decide that significant SCI does not exist simply by examining a patient who does not have any of the above symptoms, as long as the patient meets the following criteria: unaltered mental status, no neurological deficits, no intoxication from alcohol, drugs or medications and no other painful injuries that may divert his or her attention away from a SCI.

In other cases, such as when patients complain of neck pain, when they are not fully awake, or when they have obvious weakness or other signs of neurological injury, the cervical spine is kept in a rigid collar until appropriate radiological studies are completed.

Radiological Evaluation

The radiological diagnosis of SCI has traditionally begun with X-rays. In many cases, the entire spine may be X-rayed. Patients with a SCI may also receive both computerized tomography (CT or CAT scan) and magnetic resonance imaging (MRI) of the spine. In some patients, centers may proceed directly to CT scanning as the initial radiological test. For patients with known or suspected injuries, MRI is helpful for looking at the actual spinal cord itself, as well as for detecting any blood clots, herniated discs or other masses that may be compressing the spinal cord. CT scans may be helpful in visualizing the bony anatomy, including any fractures.

Even after all radiological tests have been performed, it may be advisable for a patient to wear a collar for a variable period of time. If patients are awake and alert, but still complaining of neck pain, a physician may send them home in a collar, with plans to repeat X-rays in the near future, such as in one to two weeks. The concern in these cases is that muscle spasm caused by pain might be masking an abnormal alignment of the bones in the spinal column. Once this period of spasm passes, repeat X-rays may reveal abnormal alignment or excessive motion that was not visible immediately after the injury. In patients who are comatose, confused or not fully cooperative for some other reason, adequate radiographic visualization of parts of the spine may be difficult. This is especially true of the bones at the very top of the cervical spine. In such cases, the physician may keep the patient in a collar until the patient is more cooperative. Alternatively, the physician may obtain other imaging studies to look for a radiologically-evident injury.

Treatment

Treatment of SCI begins before the patient is admitted to the hospital. Paramedics or other emergency medical services personnel carefully immobilize the entire spine at the scene of the accident. In the emergency department, this immobilization is continued while more immediate life-threatening problems are identified and addressed. If the patient must undergo emergency surgery because of trauma to the abdomen, chest or another area, immobilization and alignment of the spine are maintained during the operation.

Intensive Care Unit Treatment

If a patient has a SCI, he or she will usually be admitted to an intensive care unit (ICU). For many injuries of the cervical spine, traction may be indicated to help bring the spine into proper alignment. Standard ICU care, including maintaining a stable blood pressure, monitoring cardiovascular function, ensuring adequate ventilation and lung function and preventing and promptly treating infection and other complications, is essential so that SCI patients can achieve the best possible outcome.

Surgery

Occasionally, a surgeon may wish to take a patient to the operating room immediately if the spinal cord appears to be compressed by a herniated disc, blood clot or other lesion. This is most commonly done for patients with an incomplete SCI or with progressive neurological deterioration.

Even if surgery cannot reverse damage to the spinal cord, surgery may be needed to stabilize the spine to prevent future pain or deformity. The surgeon will decide which procedure will provide the greatest benefit to the patient.

Outcome

Persons with neurologically complete tetraplegia are at high risk for secondary medical complications. The percentages of complications for individuals with neurologically complete tetraplegia have been reported as follows:

Pressure ulcers are the most frequently observed complications, beginning at 15 percent during the first year post-injury and steadily increasing thereafter. The most common pressure ulcer location is the sacrum, the site of one third of all reported ulcers.

Source: National Spinal Cord Injury Statistical Center, University of Alabama at Birmingham, Annual Statistical Report, June 2004

Neurological Improvement

Recovery of function depends upon the severity of the initial injury. Unfortunately, those who sustain a complete SCI are unlikely to regain function below the level of injury. However, if there is some degree of improvement, it usually evidences itself within the first few days after the accident.

Incomplete injuries usually show some degree of improvement over time, but this varies with the type of injury. Although full recovery may be unlikely in most cases, some patients may be able to improve at least enough to ambulate and to control bowel and bladder function. Patients with anterior cord syndrome tend to do poorly, but many of those with Brown-Sequard syndrome can expect to reach these goals. Patients with central cord syndrome often recover to the point of being ambulatory and controlling bowel and bladder function, but they often are not able to perform detailed or intricate work with their hands.

Once a patient is stabilized, care and treatment focuses on supportive care and rehabilitation. Family members, nurses or specially trained aides all may provide supportive care. This care might include helping the patient bathe, dress, change positions to prevent bedsores and other assistance.

Rehabilitation often includes physical therapy, occupational therapy and counseling for emotional support. The services may initially be provided while the patient is hospitalized. Following hospitalization, some patients are admitted to a rehabilitation facility. Other patients can continue rehab on an outpatient basis and/or at home.

Mortality

Mortality associated with SCI is influenced by several factors. Perhaps the most important of these is the severity of associated injuries. Because of the force that is required to fracture the spine, it is not uncommon for a SCI patient to suffer significant damage to the chest and/or abdomen. Many of these associated injuries can be fatal. In general, younger patients and those with incomplete injuries have a better prognosis than older patients and those with complete injuries.

Respiratory diseases are the leading cause of death in people with SCI, pneumonia accounting for 71.2 percent of these deaths. The second and third leading causes of death, respectively, are heart disease and infections.

The cumulative 20-year survival rate for SCI patients is 70.65 percent, but due to underreporting and cases that are lost in follow-up, the mortality rates may be higher.

Source: National Spinal Cord Injury Statistical Center, University of Alabama at Birmingham, Annual Statistical Report, June 2004

SCI Prevention

While recent advances in emergency care and rehabilitation allow many SCI patients to survive, methods for reducing the extent of injury and for restoring function are still limited. Currently, there is no cure for SCI. However, ongoing research to test surgical and drug therapies continues to make progress. Drug treatments,decompression surgery,nerve cell transplantation,nerve regeneration, stem cells and complex drug therapies are all being examined in clinical trials as ways to overcome the effects of SCI. However, SCI prevention is crucial to decreasing the impact of these injuries on individual patients and on society.

Motor Vehicle Safety Tips:

Tips to Prevent Falls in the Home:

Water and Sports Safety Tips:

Firearms Safety:

SCI Resources

The AANS does not endorse any treatments, procedures, products or physicians referenced in these patient fact sheets. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific neurosurgical advice or assistance should consult his or her neurosurgeon, or locate one in your area through the AANS Find a Board-certified Neurosurgeon online tool.

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iCON Cell Therapy Platform Launched with Shipment of the 1st BERcellFLEX PODs

COLLEGE STATION, Texas, Sept. 5, 2018 /PRNewswire-PRWeb/ --Following up on the launch of the iCON Turnkey Facility Platform for a mAb manufacturing facility late last year, IPS-Integrated Project Services, LLC and G-CON Manufacturing have successfully designed and delivered the first BERcellFLEX PODs for the manufacturing of autologous cell therapies. The iCON solution provides a pre-fabricated modular cleanroom infrastructure for the drug manufacturers' requirements for both clinical and commercial manufacture of critical therapies. Following the iCON model, IPS provided the engineering design while G-CON built, tested and delivered the BERcellFLEX CAR-T processing suites in both twelve (12) foot and twenty-four (24) foot wide POD configurations.

"This is an exciting time for our companies as the iCON platform is being adopted by clients who recognize that new innovative approaches are needed to meet the growing demand for cell and gene therapy manufacturing" said Dennis Powers, Vice President of Business Development and Sales Engineering at G-CON Manufacturing Inc. "We believe that the iCON platform approach with its faster and more predictable project schedules for new facility construction are essential for supplying life changing therapies to the patients that need them."

"The gene therapy industry needs standardized solutions to meet its speed to market requirements," said Tom J. Piombino, Vice President & Process Architect at IPS. "In addition to our larger 2K mAb facility platform that we rolled out earlier this year, the BERcellFLEX12 and 24 represent a line of gene/cell therapy products that operating companies can buy today, ready-to-order, in either an open or closed-processing format with little to no engineering time we start fabricating almost immediately after URS alignment. Multiple cellFLEX units can be installed to scale up/out from Phase 1 Clinical production to Commercial Manufacturing and serve the needs of thousands of CAR-T patients per year. Being able to meet this critical need is consistent with our vision; we're thrilled to be able to offer this modular solution to help our clients get therapies to their patients."

About iCON The iCON platform, the collaborative efforts of IPS and G-CON Manufacturing, Inc., is redefining facility project execution for the biopharma industry where there is a growing need for more rapidly deployable and flexible manufacturing capability. iCON has launched turnkey designs for monoclonal antibody facilities and autologous cell therapies, and is developing platforms for cell and gene therapies, vaccines, OSD, and aseptic filling. An iCON solution can be deployed for:

About G-CON G-CON Manufacturing designs, produces and installs prefabricated cleanroom PODs. G-CON's cleanroom POD portfolio encompasses a variety of different dimensions and purposes, from laboratory environments to personalized medicine and production process platforms. The POD cleanroom units are unique from traditional cleanroom structures due to the ease of scalability, mobility and the ability to repurpose the PODs once the production process reaches the end of its lifecycle. For more information, please visit the Company's website at http://www.gconbio.com.

About IPS IPS is a global leader in developing innovative facility and bioprocess solutions for the biotechnology and pharmaceutical industries. Through operational expertise and industry-leading knowledge, skill and passion, IPS provides consulting, architecture, engineering, construction management, and compliance services that allow clients to create and manufacture life-impacting products around the world. Headquartered in Blue Bell, PA-USA, IPS is one of the largest multi-national companies servicing the life sciences industry with over 1,100 professionals in the US, Canada, Brazil, UK, Ireland, Switzerland, Singapore, China, and India. Visit our website at http://www.ipsdb.com.

2017 PR Newswire. All Rights Reserved.

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IPS and G-CON Launch iCON Cell Therapy Facility Platform ...

IPS Cell Therapy Comments Off on IPS and G-CON Launch iCON Cell Therapy Facility Platform … | September 6th, 2018

There was a very sad example of this in the last decade.There's a wonderful drug, and a class of drugs actually,but the particular drug was Vioxx, andfor people who were suffering from severe arthritis pain,the drug was an absolute lifesaver,but unfortunately, for another subset of those people,they suffered pretty severe heart side effects,and for a subset of those people, the side effects wereso severe, the cardiac side effects, that they were fatal.But imagine a different scenario,where we could have had an array, a genetically diverse array,of cardiac cells, and we could have actually testedthat drug, Vioxx, in petri dishes, and figured out,well, okay, people with this genetic type are going to havecardiac side effects, people with these genetic subgroupsor genetic shoes sizes, about 25,000 of them,are not going to have any problems.The people for whom it was a lifesavercould have still taken their medicine.The people for whom it was a disaster, or fatal,would never have been given it, andyou can imagine a very different outcome for the company,who had to withdraw the drug.

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Susan Solomon: The promise of research with stem cells ...

Cardiac Stem Cells Comments Off on Susan Solomon: The promise of research with stem cells … | August 23rd, 2018

Stem cell therapy can be described as a means or process by which stem cells are used for the prevention, treatment or the cure of diseases. Stem cells are a special kind of cells that have features other types of cells dont have. As an illustration, stem cells are capable of proliferation. This implies that they can develop into any type of cell, and grow to start performing the functions of the tissue. In addition, they can regenerate. This means they can multiply themselves. This is most important when a new tissue has to be formed. Also, they modulate immune reactions. This has made them useful for the treatment of autoimmune diseases, especially those that affect the musculoskeletal system such as rheumatoid arthritis, systemic lupus erythematosus and so on. Stem cells can be derrived from different sources. They can be extracted from the body, and in some specific parts of the body. This includes the blood, bone marrow, umbilical cord in newborns, adipose tissue, and from embryos. There are 2 main types of stem cell transplant. These are autologous stem cell transplant, and allogeneic stem cell transplant. The autologous stem cell transplant means that stem cells are extracted from the patient, processed, and then transplanted back to the patient, for therapeutic purposes. On the other hand, allogeneic stem cell transplant means the transplant of stem cells or from another individual, known as the donor, to another person, or recipient. Some treatments must be given to the receiver to prevent any cases of rejections, and other complications. The autologous is usually the most preferred type of transplant because of its almost zero side effects. Below are some of the stem cell treatments. Our goal is to provide education, research and an opportunity to connect with Stem Cell Doctors, as well as provide stem cell reviews

Adipose Stem Cell TreatmentsAdipose stem cell treatment is one of the most commonly used. This is because large quantities of stem cells can be derrived from them. According to statistics, the number of stem cells in adipose tissue are usually hundreds of times higher than what can be obtained from other sources, such as the bone marrow stem cells. Adipose stem cells have taken the center stage in the world of stem cell therapy. Apart from the ease that comes with the harvesting of these cells from the adipose tissue, they also have some special features, that separates them from other types of cells. Adipose stem cells are capable of regulating and modulating the immune system. This includes immune suppression, which is important for the treatment of autoimmune diseases. In addition, adipose stem cells can differentiate to form other types of cells. Some of them include the bone forming cells, cardiomyocytes, and cells of the nervous system.

This process can be divided into four parts. These are

Stem cell joint injection is fast becoming the new treatment of joint diseases. Stem cells derived from bone marrow, adipose and mesenchymal stem cells are the most commonly used. The stem cells are injected into the joints, and they proceed to repair and replace the damaged tissues. The cells also modulate the inflammatory process going on. Overall, stem cell joint injections significantly reduce the recovery time of patients and also eliminates pain and risks associated with surgery. Examples of diseases where this treatment is used include osteoarthritis, rheumatoid arthritis, and so on. Researchers and physicians have rated this procedure to be the future of joint therapy.

Losing a tooth as a kid isnt news because youd eventually grow them back, but losing one as an adult isnt a pleasant experience. Youd have to go through the pains of getting a replacement from your dentist. Apart from the cost of these procedures, the pain and number of days youd have to stay at home nursing the pain is also a problem. Nevertheless, there are great teeth replacement therapies available for all kinds of dental problems. Although there are already good dental treatment methods, stem cell therapy might soon become the future of dental procedures. Currently, a lot of research is being done on how stem cells can be used to develop teeth naturally, especially in patients with dental problems. The aim of the project is to develop a method whereby peoples stem cells are used in regenerating their own teeth and within the shortest time possible. Some of the benefits of the stem cell tooth would be:

The quality of life of those that underwent serious procedures, especially those that had an allogeneic hematopoietic stem cell transplantation done was studied. It was discovered that this set of people had to cope with some psychological problems, even years after the procedure. In addition, allogeneic stem cell transplantation often comes with some side effects. However, this a small price to pay, considering that the adverse effects are not usually life-threatening. Also theses types of procedures are used for severe disorders or even terminal diseases. On the other hand, autologous stem cell transplantation bears the minimum to no side effects. Patients do have a great quality of life, both in the short term and in the long term.

This is one of the many uses of stem cells. The stem cell gun is a device that is used in treating people with wounds or burns. This is done by simply triggering it, and it sprays stem cells on the affected part. This kind of treatment is crucial for victims of a severe burn. Usually, people affected by severe burns would have to endure excruciating pain. The process of recovery is usually long, which might vary from weeks to months, depending on the severity of the burn. Even after treatment, most patients are left with scars forever. However, the stem cell gun eliminates these problems, the skin can be grown back in just a matter of days. The new skin also grows evenly and blends perfectly with the other part of the body. This process is also without the scars that are usually associated with the traditional burns therapy. The stem cell gun is without any side effects.

There is one company that focuses on the production of stem cell supplements. These stem cells are usually natural ingredients that increase the development of stem cells, and also keeps them healthy. The purpose of the stem cell supplements is to help reduce the aging process and make people look younger. These supplements work by replacing the dead or repairing the damaged tissues of the body. There have been a lot of testimonials to the efficacy of these supplements.

It is the goal of researchers to make stem cell therapy a good alternative for the millions of patients suffering from cardiac-related diseases. According to some experiments carried out in animals, stem cells were injected into the ones affected by heart diseases. A large percentage of them showed great improvement, even within just a few weeks. However, when the trial was carried out in humans, some stem cells went ahead to develop into heart muscles, but overall, the heart function was generally improved. The reason for the improvement has been attributed to the formation of new vessels in the heart. The topic that has generated a lot of arguments have been what type of cells should be used in the treatment of heart disorders. Stem cells extracted from the bone marrow, embryo have been in use, although bone marrow stem cells are the most commonly used. Stem cells extracted from bone marrow can differentiate into cardiac cells, while studies have shown that other stem cells cannot do the same. Even though the stem cell therapy has a lot of potential in the future, more research and studies have to be done to make that a reality.

The use of stem cells for the treatment of hair loss has increased significantly. This can be attributed to the discovery of stem cells in bone marrow, adipose cells, umbilical cord, and so on. Stem cells are extracted from the patient, through any of the sources listed above. Adipose tissue stem cells are usually the most convenient in this scenario, as they do not require any special extraction procedure. Adipose tissue is harvested from the abdominal area. The stem cells are then isolated from the other cells through a process known as centrifugation. The stem cells are then activated and are now ready for use. The isolated stem cells are then introduced into the scalp, under local anesthesia. The entire process takes about three hours. Patients are free to go home, after the procedure. Patients would begin to see improvements in just a few months, however, this depends largely on the patients ability to heal. Every patient has a different outcome.

Human umbilical stem cells are cells extracted from the umbilical cord of a healthy baby, shortly after birth. Umbilical cord tissue is abundant in stem cells, and the stem cells can differentiate into many types of cells such as red blood cells, white blood cells, and platelets. They are also capable of differentiating into non-blood cells such as muscle cells, cartilage cells and so on. These cells are usually preferred because its' extraction is minimally non invasive. It also is nearly painless. It also has zero risks of rejecting, as it does not require any form of matching or typing.Human umbilical stem cell injections are used for the treatment of spinal cord injuries. A trial was done on twenty-five patients that had late-stage spinal cord injuries. They were placed on human umbilical stem cell therapy, while another set of 25 patients were simultaneously placed on the usual rehabilitation therapy. The two groups were studied for the next twelve months. The results of the trial showed that those people placed on stem cell therapy by administering the human umbilical cell tissue injections had a significant recovery, as compared to the other group that underwent the traditional rehabilitation therapy. It was concluded that human umbilical tissue injections applied close to the injured part gives the best outcomes.

Stem cell therapy has been used for the treatment of many types diseases. This ranges from terminal illnesses such as cancer, joint diseases such as arthritis, and also autoimmune diseases. Stem cell therapy is often a better alternative to most traditional therapy today. This is because stem cell procedure is minimally invasive when compared to chemotherapy and so on. It harnesses the bodys own ability to heal. The stem cells are extracted from other parts of the body and then transplanted to other parts of the body, where they would repair and maintain the tissues. They also perform the function of modulating the immune system, which makes them important for the treatment of autoimmune diseases. Below are some of the diseases that stem cell therapies have been used successfully:

A stem cell bank can be described as a facility where stem cells are stored for future purposes. These are mostly amniotic stem cells, which are derived from the amnion fluid. Umbilical cord stem cells are also equally important as it is rich in stem cells and can be used for the treatment of many diseases. Examples of these diseases include cancer, blood disorders, autoimmune diseases, musculoskeletal diseases and so on. According to statistics, umbilical stem cells can be used for the treatment of over eighty diseases. Storing your stem cells should be seen as an investment in your health for future sake. Parents do have the option of either throwing away their babys umbilical cord or donating it to stem cell banks.

The adipose tissue contains a lot of stem cells, that has the ability to transform into other cells such as muscle, cartilage, neural cells. They are also important for the treatment of some cardiovascular diseases. This is what makes it important for people to want to store their stem cells. The future health benefit is huge. The only way adults can store their stem cells in sufficient amounts is to extract the stem cells from their fat tissues. This process is usually painless and fast. Although, the extraction might have to be done between 3 to 5 times before the needed quantity is gotten. People that missed the opportunity to store their stem cells, using their cord cells, can now store it using their own adipose tissues. This can be used at any point in time.

Side effects often accompany every kind of treatment. However, this depends largely on the individual. While patients might present with side effects, some other people wouldnt. Whether a patient will present with adverse effects, depends on the following factors;

Some of the common side effects of stem cell transplant are;

Stem cell treatment has been largely successful so far, however, more studies and research needs to be done. Stem cell therapy could be the future.

Stem cells are unique cells that have some special features such as self-regeneration, tissue repair, and modulation of the immune system. These are the features that are employed in the treatment of diseases.

Our doctors are certified by iSTEMCELL but operate as part of a medical group or as independent business owners and as such are free to charge what the feel to be the right fit for their practice and clients. We have seen Stem Cell Treatment costs range from $3500 upwards of $30,000 depending on the condition and protocol required for intended results. Find the Best Stem Cell Doctor Near me If you are interested in saving money, try our STEM CELL COUPON!

Travel Medcations are becoming very popular around the globe for several reasons but not for what one might think. It is not about traveling to Mexico to save money, but to get procedures or protocols that are not yet available in your home country. Many procedures are started in your home country, then the tissue is set to the tissue lab where it is then grown in a process to maximize live cells, then sent to a hospital in Mexico designed to treat or provide different therapies for different conditions. If you're ready to take a medical vacation call 972-800-6670 for our"WHITE GLOVE" service.

Chen, C. and Hou, J. (2016). Mesenchymal stem cell-based therapy in kidney transplantation. Stem Cell Research & Therapy, 7(1).

Donnelly, A., Johar, S., OBrien, T. and Tuan, R. (2010). Welcome to Stem Cell Research & Therapy. Stem Cell Research & Therapy, 1(1), p.1.

Groothuis, S. (2015). Changes in Stem Cell Research. Stem Cell Research, 14(1), p.130.

Rao, M. (2012). Stem cells and regenerative medicine. Stem Cell Research & Therapy, 3(4), p.27.

Vunjak-Novakovic, G. (2013). Physical influences on stem cells. Stem Cell Research & Therapy, 4(6), p.153.

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Stem Cell Therapy and Stem Cell Injection Provider Finder ...

Cardiac Stem Cells Comments Off on Stem Cell Therapy and Stem Cell Injection Provider Finder … | August 19th, 2018

Dublin, Aug. 02, 2018 (GLOBE NEWSWIRE) -- The "Global Induced Pluripotent Stem Cell (iPS Cell) Industry Report 2018-19" report has been added to ResearchAndMarkets.com's offering.

Groundbreaking experimentation in 2006 led to the introduction of induced pluripotent stem cells (iPSCs). These are adult cells which are isolated and then transformed into embryonic-like stem cells through the manipulation of gene expression, as well as other methods. Research and experimentation using mouse cells by Shinya Yamanaka's lab at Kyoto University in Japan was the first instance in which there was a successful generation of iPSCs.

In 2007, a series of follow-up experiments were done at Kyoto University in which human adult cells were transformed into iPSCs. Nearly simultaneously, a research group led by James Thomson at the University of Wisconsin-Madison accomplished the same feat of deriving iPSC lines from human somatic cells.

Since the discovery of iPSCs a large and thriving research product market has grown into existence, largely because the cells are non-controversial and can be generated directly from adult cells. While it is clear that iPSCs represent a lucrative product market, methods for commercializing this cell type are still being explored, as clinical studies investigating iPSCs continue to increase in number.

iPS Cell Therapies

2013 was a landmark year in Japan because it saw the first cellular therapy involving the transplant of iPS cells into humans initiated at the RIKEN Center in Kobe, Japan. Led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB). Dr. Takahashi was investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration.

Although the study was suspended in 2015 due to safety concerns, in June 2016 RIKEN Institute announced that it would resume the clinical study using allogeneic rather than autologous iPSC-derived cells, because of the cost and time efficiencies.

In a world-first, Cynata Therapeutics received approval in September 2016 to launch the world's first formal clinical trial of an allogeneic iPSC-derived cell product, called CYP-001. The study involves centers in the UK and Australia. In this trial, Cynata is testing an iPS cell-derived mesenchymal stem cell (MSC) product for the treatment of GvHD.

On 16 May 2018, Nature News then reported that Japan's health ministry gave doctors at Osaka University permission to take sheets of tissue derived from iPS cells and graft them onto diseased human hearts. The team of Japanese doctors, led by cardiac surgeon Yoshiki Sawa at Osaka University, will use iPS cells to create a sheet of 100 million heart-muscle cells. From preclinical studies in pigs, the medical team determined that thin sheets of cell grafts can improve heart function, likely through paracrine signaling.

Kyoto University Hospital in Kobe, Japan also stated it would be opening an iPSC therapy center in 2019, for purposes of conducting clinical studies on iPS cell therapies. Officials for Kyoto Hospital said it will open a 30-bed ward to test the efficacy and safety of the therapies on volunteer patients, with the hospital aiming to initiate construction at the site in February of 2016 and complete construction by September 2019.

iPS Cell Market Competitors

In 2009 ReproCELL, a company established as a venture company originating from the University of Tokyo and Kyoto University was the first to make iPSC products commercially available with the launch of its human iPSC-derived cardiomyocytes, which it called ReproCario.

Cellular Dynamics International, a Fujifilm company, is another major market player in the iPSC sector. Similar to ReproCELL, CDI established its control of the iPSC industry after being founded in 2004 by Dr. James Thomson at the University of Wisconsin-Madison, who in 2007 derived iPSC lines from human somatic cells for the first time ever (the feat was accomplished simultaneously by Dr. Shinya Yamanaka's lab in Japan).

A European leader within the iPSC market is Ncardia, formed through the merger of Axiogenesis and Pluriomics. Founded in 2001 and headquartered in Cologne, Germany, Axiogenesis initially focused on generating mouse embryonic stem cell-derived cells and assays. After Yamanaka's groundbreaking iPSC technology became available, Axiogenesis was the first European company to license and adopt Yamanaka's iPSC technology in 2010.

Ncardia's focus lies on preclinical drug discovery and drug safety through the development of functional assays using human neuronal and cardiac cells, although it is expanding into new areas. Its flagship offering is its Cor.4U human cardiomyocyte product family, including cardiac fibroblasts.

In summary, market leaders have emerged in all areas of iPSC development, including:

iPS Cell Commercialization

Key Findings

Key Topics Covered

1. SCOPE AND METHODOLOGY

2. EXECUTIVE SUMMARY

3. BACKGROUND - iPSC RESEARCH

4. MARKET ANALYSIS BY PRODUCT CATEGORY

5. MARKET ANALYSIS BY APPLICATION

6. MARKET ANALYSIS BY GEOGRAPHY

7. PATENTS

8. COMPANIES

9. COMPANY PROFILES

10. CONCLUSIONS

For more information about this report visit https://www.researchandmarkets.com/research/njhzjc/induced?w=12

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Induced Pluripotent Stem Cell (iPS Cell): 2018-2022 ...

IPS Cell Therapy Comments Off on Induced Pluripotent Stem Cell (iPS Cell): 2018-2022 … | August 5th, 2018

If you or a loved one will be having a bone marrow transplant or donating stem cells, what does it entail? What are the different types of bone marrow transplants and what is the experience like for both the donor and recipient?

A bone marrow transplant is a procedure in which when special cells (called stem cells) are removed from the bone marrow or peripheral blood, filtered and given back either to the same person or to another person.

Since we now derive most stem cells needed from the blood rather than the bone marrow, a bone marrow transplant is now more commonly referred to as stem cell transplant.

Bone marrow is found in larger bones in the body such as the pelvic bones. This bone marrow is the manufacturing site for stem cells. Stem cells are "pluripotential" meaning that the cells are the precursor cells which can evolve into the different types of blood cells, such as white blood cells, red blood cells, and platelets.

If something is wrong with the bone marrow or the production of blood cells is decreased, a person can become very ill or die. In conditions such as aplastic anemia, the bone marrow stops producing blood cells needed for the body. In diseases such as leukemia, the bone marrow produces abnormal blood cells.

The purpose of a bone marrow transplant is thus to replace cells not being produced or replace unhealthy stem cells with healthy ones. This can be used to treat or even cure the disease.

In addition to leukemias, lymphomas, and aplastic anemia, stem cell transplants are being evaluated for many disorders, ranging from solid tumors to other non-malignant disorders of the bone marrow, to multiple sclerosis.

There are two primary types of bone marrow transplants, autologous and allogeneic transplants.

The Greek prefix "auto" means "self." In an autologous transplant, the donor is the person who will also receive the transplant. This procedure, also known as a "rescue transplant" involves removing your stem cells and freezing them. You then receive high dose chemotherapy followed by infusion of the thawed out frozen stem cells. It may be used to treat leukemias, lymphomas, or multiple myeloma.

The Greek prefix "allo" means "different" or "other." In an allogeneic bone marrow transplant, the donor is another person who has a genetic tissue type similar to the person needing the transplant. Because tissue types are inherited, similar to hair color or eye color, it is more likely that you will find a suitable donor in a family member, especially a sibling. Unfortunately, this occurs only 25 to 30 percent of the time.

If a family member does not match the recipient, the National Marrow Donor Program Registry database can be searched for an unrelated individual whose tissue type is a close match. It is more likely that a donor who comes from the same racial or ethnic group as the recipient will have the same tissue traits. Learn more about finding a donor for a stem cell transplant.

Bone marrow cells can be obtained in three primary ways. These include:

The majority of stem cell transplants are done using PBSC collected by apheresis (peripheral blood stem cell transplants.) This method appears to provide better results for both the donor and recipient. There still may be situations in which a traditional bone marrow harvest is done.

Donating stem cells or bone marrow is fairly easy. In most cases, a donation is made using circulating stem cells (PBSC) collected by apheresis. First, the donor receives injections of a medication for several days that causes stem cells to move out of the bone marrow and into the blood. For the stem cell collection, the donor is connected to a machine by a needle inserted in the vein (like for donating blood). Blood is taken from the vein, filtered by the machine to collect the stem cells, then returned back to the donor through a needle in the other arm. There is almost no need for a recovery time with this procedure.

If stem cells are collected by bone marrow harvest (much less likely), the donor will go to the operating room and while asleep under anesthesia and a needle will be inserted into either the hip or the breastbone to take out some bone marrow. After awakening, there may be some pain where the needle was inserted.

A bone marrow transplant can be a very challenging procedure for the recipient.

The first step is usually receiving high doses of chemotherapy and/or radiation to eliminate whatever bone marrow is present. For example, with leukemia, it is first important to remove all of the abnormal bone marrow cells.

Once a person's original bone marrow is destroyed, the new stem cells are injected intravenously, similar to a blood transfusion. The stem cells then find their way to the bone and start to grow and produce more cells (called engraftment).

There are many potential complications. The most critical time is usually when the bone marrow is destroyed so that few blood cells remain. Destruction of the bone marrow results in greatly reduced numbers of all of the types of blood cells (pancytopenia). Without white blood cells there is a serious risk of infection, and infection precautions are used in the hospital (isolation). Low levels of red blood cells (anemia) often require blood transfusions while waiting for the new stem cells to begin growing. Low levels of platelets (thrombocytopenia) in the blood can lead to internal bleeding.

A common complication affecting 40 to 80 percent of recipients is graft versus host disease. This occurs when white blood cells (T cells) in the donated cells (graft) attack tissues in the recipient (the host), and can be life-threatening.

An alternative approach referred to as a non-myeloablative bone marrow transplant or "mini-bone marrow transplant" is somewhat different. In this procedure, lower doses of chemotherapy are given that do not completely wipe out or "ablate" the bone marrow as in a typical bone marrow transplant. This approach may be used for someone who is older or otherwise might not tolerate the traditional procedure. In this case, the transplant works differently to treat the disease as well. Instead of replacing the bone marrow, the donated marrow can attack cancerous cells left in the body in a process referred to as "graft versus malignancy."

If you'd like to become a volunteer donor, the process is straightforward and simple. Anyone between the ages of 18 and 60 and in good health can become a donor. There is a form to fill out and a blood sample to give; you can find all the information you need at the National Marrow Donor Programwebsite. You can join a donor drive in your area or go to a local Donor Center to have the blood test done.

When a person volunteers to be a donor, his or her particular blood tissue traits, as determined by a special blood test (histocompatibility antigen test,) are recorded in the Registry. This "tissue typing" is different from a person's A, B, or O blood type. The Registry record also contains contact information for the donor, should a tissue type match be made.

Bone marrow transplants can be either autologous (from yourself) or allogeneic (from another person.) Stem cells are obtained either from peripheral blood, a bone marrow harvest or from cord blood that is saved at birth.

For a donor, the process is relatively easy. For the recipient, it can be a long and difficult process, especially when high doses of chemotherapy are needed to eliminate bone marrow. Complications are common and can include infections, bleeding, and graft versus host disease among others.

That said, bone marrow transplants can treat and even cure some diseases which had previously been almost uniformly fatal. While finding a donor was more challenging in the past, the National Marrow Donor Program has expanded such that many people without a compatible family member are now able to have a bone marrow/stem cell transplant.

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How Bone Marrow and Stem Cell Transplants Work

Bone Marrow Stem Cells Comments Off on How Bone Marrow and Stem Cell Transplants Work | August 3rd, 2018

"Muscle fiber" and "Myofiber" redirect here. For protein structures inside cells, see Myofibril.

A myocyte (also known as a muscle cell)[1] is the type of cell found in muscle tissue. Myocytes are long, tubular cells that develop from myoblasts to form muscles in a process known as myogenesis.[2] There are various specialized forms of myocytes: cardiac, skeletal, and smooth muscle cells, with various properties. The striated cells of cardiac and skeletal muscles are referred to as muscle fibers.[3] Cardiomyocytes are the muscle fibres that form the chambers of the heart, and have a single central nucleus.[4] Skeletal muscle fibers help support and move the body and tend to have peripheral nuclei.[5][6] Smooth muscle cells control involuntary movements such as the peristalsis contractions in the oesophagus and stomach.

The unusual microstructure of muscle cells has led cell biologists to create specialized terminology. However, each term specific to muscle cells has a counterpart that is used in the terminology applied to other types of cells:

The sarcoplasm is the cytoplasm of a muscle fiber. Most of the sarcoplasm is filled with myofibrils, which are long protein cords composed of myofilaments. The sarcoplasm is also composed of glycogen, a polysaccharide of glucose monomers, which provides energy to the cell with heightened exercise, and myoglobin, the red pigment that stores oxygen until needed for muscular activity.[7]

There are three types of myofilaments:[7]

Together, these myofilaments work to produce a muscle contraction.

The sarcoplasmic reticulum, a specialized type of smooth endoplasmic reticulum, forms a network around each myofibril of the muscle fiber. This network is composed of groupings of two dilated end-sacs called terminal cisternae, and a single transverse tubule, or T tubule, which bores through the cell and emerge on the other side; together these three components form the triads that exist within the network of the sarcoplasmic reticulum, in which each T tubule has two terminal cisternae on each side of it. The sarcoplasmic reticulum serves as reservoir for calcium ions, so when an action potential spreads over the T tubule, it signals the sarcoplasmic reticulum to release calcium ions from the gated membrane channels to stimulate a muscle contraction.[7][8]

The sarcolemma is the cell membrane of a striated muscle fiber and receives and conducts stimuli. At the end of each muscle fiber, the outer layer of the sarcolemma combines with tendon fibers.[9] Within the muscle fiber pressed against the sarcolemma are multiple flattened nuclei; this multinuclear condition results from multiple myoblasts fusing to produce each muscle fiber, where each myoblast contributes one nucleus.[7]

The cell membrane of a myocyte has several specialized regions, which may include the intercalated disk and the transverse tubular system. The cell membrane is covered by a lamina coat which is approximately 50nm wide. The laminar coat is separable into two layers; the lamina densa and lamina lucida. In between these two layers can be several different types of ions, including calcium.[10]

The cell membrane is anchored to the cell's cytoskeleton by anchor fibers that are approximately 10nm wide. These are generally located at the Z lines so that they form grooves and transverse tubules emanate. In cardiac myocytes this forms a scalloped surface.[10]

The cytoskeleton is what the rest of the cell builds off of and has two primary purposes; the first is to stabilize the topography of the intracellular components and the second is to help control the size and shape of the cell. While the first function is important for biochemical processes, the latter is crucial in defining the surface to volume ratio of the cell. This heavily influences the potential electrical properties of excitable cells. Additionally deviation from the standard shape and size of the cell can have negative prognostic impact.[10]

Each muscle fiber contains myofibrils, which are very long chains of sarcomeres, the contractile units of the cell. A cell from the biceps brachii muscle may contain 100,000 sarcomeres.[11][verification needed] The myofibrils of smooth muscle cells are not arranged into sarcomeres. The sarcomeres are composed of thin and thick filaments. Thin filaments are made of actin and attach at Z lines which help them line up correctly with each other.[12] Troponins are found at intervals along the thin filaments. Thick filaments are made of the elongated protein myosin.[13] The sarcomere does not contain organelles or a nucleus. Sarcomeres are marked by Z lines which show the beginning and the end of a sarcomere. Individual myocytes are surrounded by endomysium.

Myocytes are bound together by perimysium into bundles called fascicles; the bundles are then grouped together to form muscle tissue, which is enclosed in a sheath of epimysium. The perimysium contains blood vessels and nerves which provide for the muscle fibers. Muscle spindles are distributed throughout the muscles and provide sensory feedback information to the central nervous system. Myosin is shaped like a long shaft with a rounded end pointed out towards the surface. This structure forms the cross bridge that connects with the thin filaments.[13]

A myoblast is a type of embryonic progenitor cell that differentiates to give rise to muscle cells.[14] Differentiation is regulated by myogenic regulatory factors, including MyoD, Myf5, myogenin, and MRF4.[15] GATA4 and GATA6 also play a role in myocyte differentiation.[16]

Skeletal muscle fibers are made when myoblasts fuse together; muscle fibers therefore are cells with multiple nuclei, known as myonuclei, with each cell nucleus originating from a single myoblast. The fusion of myoblasts is specific to skeletal muscle (e.g., biceps brachii) and not cardiac muscle or smooth muscle.

Myoblasts in skeletal muscle that do not form muscle fibers dedifferentiate back into myosatellite cells. These satellite cells remain adjacent to a skeletal muscle fiber, situated between the sarcolemma and the basement membrane[17] of the endomysium (the connective tissue investment that divides the muscle fascicles into individual fibers). To re-activate myogenesis, the satellite cells must be stimulated to differentiate into new fibers.

Myoblasts and their derivatives, including satellite cells, can now be generated in vitro through directed differentiation of pluripotent stem cells.[18]

Kindlin-2 plays a role in developmental elongation during myogenesis.[19]

Muscle fibers grow when exercised and shrink when not in use. This is due to the fact that exercise stimulates the increase in myofibrils which increase the overall size of muscle cells. Well exercised muscles can not only add more size but can also develop more mitochondria, myoglobin, glycogen and a higher density of capillaries. However muscle cells cannot divide to produce new cells, and as a result we have fewer muscle cells as an adult than a newborn.[20]

When contracting, thin and thick filaments slide with respect to each other by using adenosine triphosphate. This pulls the Z discs closer together in a process called sliding filament mechanism. The contraction of all the sarcomeres results in the contraction of the whole muscle fiber. This contraction of the myocyte is triggered by the action potential over the cell membrane of the myocyte. The action potential uses transverse tubules to get from the surface to the interior of the myocyte, which is continuous within the cell membrane. Sarcoplasmic reticula are membranous bags that transverse tubules touch but remain separate from. These wrap themselves around each sarcomere and are filled with Ca2+.[13]

Excitation of a myocyte causes depolarization at its synapses, the neuromuscular junctions, which triggers action potential. With a singular neuromuscular junction, each muscle fiber receives input from just one somatic efferent neuron. Action potential in a somatic efferent neuron causes the release of the neurotransmitter acetylcholine.[21]

When the acetylcholine is released it diffuses across the synapse and binds to a receptor on the sarcolemma, a term unique to muscle cells that refers to the cell membrane. This initiates an impulse that travels across the sarcolemma.[20]

When the action potential reaches the sarcoplasmic reticulum it triggers the release of Ca2+ from the Ca2+ channels. The Ca2+ flows from the sarcoplasmic reticulum into the sarcomere with both of its filaments. This causes the filaments to start sliding and the sarcomeres to become shorter. This requires a large amount of ATP, as it is used in both the attachment and release of every myosin head. Very quickly Ca2+ is actively transported back into the sarcoplasmic reticulum, which blocks the interaction between the thin and thick filament. This in turn causes the muscle cell to relax.[20]

There are four main different types of muscle contraction: twitch, treppe, tetanus and isometric/isotonic. Twitch contraction is the process previously described, in which a single stimulus signals for a single contraction. In twitch contraction the length of the contraction may vary depending on the size of the muscle cell. During treppe (or summation) contraction muscles do not start at maximum efficiency; instead they achieve increased strength of contraction due to repeated stimuli. Tetanus involves a sustained contraction of muscles due to a series of rapid stimuli, which can continue until the muscles fatigue. Isometric contractions are skeletal muscle contractions that do not cause movement of the muscle. However, isotonic contractions are skeletal muscle contractions that do cause movement.[20]

Specialized cardiomyocytes located in the sinoatrial node are responsible for generating the electrical impulses that control the heart rate. These electrical impulses coordinate contraction throughout the remaining heart muscle via the electrical conduction system of the heart. Sinoatrial node activity is modulated, in turn, by nerve fibres of both the sympathetic and parasympathetic nervous systems. These systems act to increase and decrease, respectively, the rate of production of electrical impulses by the sinoatrial node.

There are numerous methods employed for fiber-typing, and confusion between the methods is common among non-experts. Two commonly confused methods are histochemical staining for myosin ATPase activity and immunohistochemical staining for Myosin heavy chain (MHC) type. Myosin ATPase activity is commonlyand correctlyreferred to as simply "fiber type", and results from the direct assaying of ATPase activity under various conditions (e.g. pH).[22] Myosin heavy chain staining is most accurately referred to as "MHC fiber type", e.g. "MHC IIa fibers", and results from determination of different MHC isoforms.[22] These methods are closely related physiologically, as the MHC type is the primary determinant of ATPase activity. Note, however, that neither of these typing methods is directly metabolic in nature; they do not directly address oxidative or glycolytic capacity of the fiber. When "type I" or "type II" fibers are referred to generically, this most accurately refers to the sum of numerical fiber types (I vs. II) as assessed by myosin ATPase activity staining (e.g. "type II" fibers refers to type IIA + type IIAX + type IIXA... etc.).

Below is a table showing the relationship between these two methods, limited to fiber types found in humans. Note the sub-type capitalization used in fiber typing vs. MHC typing, and that some ATPase types actually contain multiple MHC types. Also, a subtype B or b is not expressed in humans by either method.[23] Early researchers believed humans to express a MHC IIb, which led to the ATPase classification of IIB. However, later research showed that the human MHC IIb was in fact IIx,[23] indicating that the IIB is better named IIX. IIb is expressed in other mammals, so is still accurately seen (along with IIB) in the literature. Non human fiber types include true IIb fibers, IIc, IId, etc.

Further fiber typing methods are less formally delineated, and exist on more of a spectrum. They tend to be focused more on metabolic and functional capacities (i.e., oxidative vs. glycolytic, fast vs. slow contraction time). As noted above, fiber typing by ATPase or MHC does not directly measure or dictate these parameters. However, many of the various methods are mechanistically linked, while others are correlated in vivo.[26][27] For instance, ATPase fiber type is related to contraction speed, because high ATPase activity allows faster crossbridge cycling.[22] While ATPase activity is only one component of contraction speed, type I fibers are "slow", in part, because they have low speeds of ATPase activity in comparison to type II fibers. However, measuring contraction speed is not the same as ATPase fiber typing.

Because of these types of relationships, Type I and Type II fibers have relatively distinct metabolic, contractile, and motor-unit properties. The table below differentiates these types of properties. These types of propertieswhile they are partly dependent on the properties of individual fiberstend to be relevant and measured at the level of the motor unit, rather than individual fiber.[22]

Traditionally, fibers were categorized depending on their varying color, which is a reflection of myoglobin content. Type I fibers appear red due to the high levels of myoglobin. Red muscle fibers tend to have more mitochondria and greater local capillary density. These fibers are more suited for endurance and are slow to fatigue because they use oxidative metabolism to generate ATP (adenosine triphosphate). Less oxidative type II fibers are white due to relatively low myoglobin and a reliance on glycolytic enzymes.

Fibers can also be classified on their twitch capabilities, into fast and slow twitch. These traits largely, but not completely, overlap the classifications based on color, ATPase, or MHC.

Some authors define a fast twitch fiber as one in which the myosin can split ATP very quickly. These mainly include the ATPase type II and MHC type II fibers. However, fast twitch fibers also demonstrate a higher capability for electrochemical transmission of action potentials and a rapid level of calcium release and uptake by the sarcoplasmic reticulum. The fast twitch fibers rely on a well-developed, short term, glycolytic system for energy transfer and can contract and develop tension at 23 times the rate of slow twitch fibers. Fast twitch muscles are much better at generating short bursts of strength or speed than slow muscles, and so fatigue more quickly.[28]

The slow twitch fibers generate energy for ATP re-synthesis by means of a long term system of aerobic energy transfer. These mainly include the ATPase type I and MHC type I fibers. They tend to have a low activity level of ATPase, a slower speed of contraction with a less well developed glycolytic capacity. They contain high mitochondrial volumes, and the high levels of myoglobin that give them a red pigmentation. They have been demonstrated to have high concentrations of mitochondrial enzymes, thus they are fatigue resistant. Slow twitch muscles fire more slowly than fast twitch fibers, but are able to contract for a longer time before fatiguing.[28]

Individual muscles tend to be a mixture of various fiber types, but their proportions vary depending on the actions of that muscle and the species. For instance, in humans, the quadriceps muscles contain ~52% type I fibers, while the soleus is ~80% type I.[29] The orbicularis oculi muscle of the eye is only ~15% type I.[29] Motor units within the muscle, however, have minimal variation between the fibers of that unit. It is this fact that makes the size principal of motor unit recruitment viable.

The total number of skeletal muscle fibers has traditionally been thought not to change.It is believed there are no sex or age differences in fiber distribution; however, proportions of fiber types vary considerably from muscle to muscle and person to person.Sedentary men and women (as well as young children) have 45% type II and 55% type I fibers.[citation needed]People at the higher end of any sport tend to demonstrate patterns of fiber distribution e.g. endurance athletes show a higher level of type I fibers.Sprint athletes, on the other hand, require large numbers of type IIX fibers.Middle distance event athletes show approximately equal distribution of the two types. This is also often the case for power athletes such as throwers and jumpers.It has been suggested that various types of exercise can induce changes in the fibers of a skeletal muscle.[30]It is thought that if you perform endurance type events for a sustained period of time, some of the type IIX fibers transform into type IIA fibers. However, there is no consensus on the subject.It may well be that the type IIX fibers show enhancements of the oxidative capacity after high intensity endurance training which brings them to a level at which they are able to perform oxidative metabolism as effectively as slow twitch fibers of untrained subjects. This would be brought about by an increase in mitochondrial size and number and the associated related changes, not a change in fiber type.

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1. Cellular Dynamics International, Owned by FujiFilm Holdings

Founded in 2004 and listed on NASDAQ in July 2013, Cellular Dynamics International (CDI) is headquartered in Madison, Wisconsin. The company is known for its extremely robust patent portfolio containing more than 900 patents.

According to the company, CDI is the worlds largest producer of fully functional human cells derived from induced pluripotent stem (iPS) cells.[1] Their trademarked, iCell Cardiomyocytes, derived from iPSCs, are human cardiac cells used to aid drug discovery, improve the predictability of a drugs worth, and screen for toxicity. In addition, CDI provides: iCell Endothelial Cells for use in vascular-targeted drug discovery and tissue regeneration, iCell Hepatocytes, and iCell Neurons for pre-clinical drug discovery, toxicity testing, disease prediction, and cellular research.[2]

Induced pluripotent stem cells were first produced in 2006 from mouse cells and in 2007 from human cells, by Shinya Yamanaka at Kyoto University,[3] who also won the Nobel Prize in Medicine or Physiology for his work on iPSCs.[4] Yamanaka has ties to Cellular Dynamics International as a member of the scientific advisory board of iPS Academia Japan. IPS Academia Japan was originally established to manage the patents and technology of Yamanakas work, and is now the distributor of several of Cellular Dynamics products, including iCell Neurons, iCell Cardiomyocytes, and iCell Endothelial Cells.[5]

Importantly, in 2010 Cellular Dynamics became the first foreign company to be granted rights to use Yamanakas iPSC patent portfolio. Not only has CDI licensed rights to Yamanakas patents, but it also has a license to use Otsu, Japan-based Takara Bios RetroNectin product, which it uses as a tool to produce its iCell and MyCell products.[6]

Furthermore, in February 2015, Cellular Dynamics International announced it would be manufacturing cGMP HLA Superdonor stem cell lines that will support cellular therapy applications through genetic matching.[8] Currently, CDI has two HLA super donor cell lines that provide a partial HLA match to approximately 19% of the population within the U.S., and it aims to expand its master stem cell bank by collecting more donor cell lines that will cover 95% of the U.S. population.[9] The HLA super donor cell lines were manufactured using blood samples and used to produce pluripotent iPSC lines, giving the cells the capacity to differentiate into nearly any cell within the human body.

On March 30, 2015, Fujifilm Holdings Corporation announced that it was acquiring CDI for $307 million, allowing CDI to continue to run its operations in Madison, Wisconsin, and Novato, California as a consolidated subsidiary of Fujifilm.[14] A key benefit of the merger is that CDIs technology platform enables the production of high-quality fully functioning iPSCs (and other human cells) on an industrial scale, while Fujifilm has developed highly-biocompatible recombinant peptides that can be shaped into a variety of forms for use as a cellular scaffold in regenerative medicine when used in conjunction with CDIs products.[15]

Additionally, Fujifilm has been strengthening its presence in the regenerative medicine field over the past several years, including a recent A$4M equity stake in Cynata Therapeutics and an acquisition of Japan Tissue Engineering Co. Ltd. in December 2014. Most commonly called J-TEC, Japan Tissue Engineering Co. Ltd. successfully launched the first two regenerative medicine products in the country of Japan. According to Kaz Hirao, CEO of CDI, It is very important for CDI to get into the area of therapeutic products, and we can accelerate this by aligning it with strategic and technical resources present within J-TEC.

Kaz Hirao also states, For our Therapeutic businesses, we will aim to file investigational new drugs (INDs) with the U.S. FDA for the off-the-shelf iPSC-derived allogeneic therapeutic products. Currently, we are focusing on retinal diseases, heart disorders, Parkinsons disease, and cancers. For those four indicated areas, we would like to file several INDs within the next five years.

Finally, in September 2015, CDI again strengthened its iPS cell therapy capacity by setting up a new venture, Opsis Therapeutics. Opsis is focused on discovering and developing novel medicines to treat retinal diseases and is a partnership with Dr. David Gamm, the pioneer of iPS cell-derived retinal differentiation and transplantation.

In summary, several key events indicate CDIs commitment to developing iPS cell therapeutics, including:

Australian stem cell company Cynata Therapeutics (ASX:CYP) is taking a unique approach by creating allogeneic iPSC derived mesenchyal stem cell (MSCs) on a commercial scale. Cynatas Cymerus technology utilizes iPSCs provided by Cellular Dynamics International, a Fujifilm company, as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-grade MSCs. According to Cynatas Executive Chairman Stewart Washer who was interviewed by The Life Sciences Report, The Cymerus technology gets around the loss of potency with the unlimited iPS cellor induced pluripotent stem cellwhich is basically immortal.

On January 19, 2017, Fujifilm took an A$3.97 million (10%) strategic equity stake in Cynata, positioning the parties to collaborate on the further development and commercialization of Cynatas lead Cymerus therapeutic MSC product CYP-001 for graft-versus-host disease (GvHD). (CYP-001 is the product designation unique to the GVHD indication). The Fujifilm partnership also includes potential future upfront and milestone payments in excess of A$60 million and double-digit royalties on CYP-001 product net sales for Cynata Therapeutics, as well as a strategic relationship for the potential future manufacture of CYP-001 and certain rights to other Cynata technology.

One of the key inventors of Cynatas technology is Igor Slukvin, MD, Ph.D., Scientific Founder of Cellular Dynamics International (CDI) and Cynata Therapeutics. Dr. Slukvin has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvins co-inventor is Dr. James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human induced pluripotent stem cell (hiPSC). Dr. James Thompson was the Founder of CDI in 2004.

There are three strategic connections between Cellular Dynamics International (CDI) and Cynata Therapeutics, which include:

Recently, Cynata received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved, titled An Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease. It will be the worlds first clinical trial involving a therapeutic product derived from allogeneic (unrelated to the patient) induced pluripotent stem cells (iPSCs).

Participants for Cynatas upcoming Phase I clinical trial will be adults who have undergone an allogeneic haematopoietic stem cell transplant (HSCT) to treat a hematological disorder and subsequently been diagnosed with steroid-resistant Grade II-IV GvHD. The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.

Using Professor Yamanakas Nobel Prize-winning achievement of ethically uncontentious iPSCs and CDIs high-quality iPSCs as source material, Cynata has achieved two world firsts:

Cynata has also released promising pre-clinical data in Asthma, Myocardial Infarction (Heart Attack), and Critical Limb Ischemia.

There are four key advantages of Cynatas proprietary Cymerus MSC manufacturing platform. Because the proprietary Cymerus technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.

Finally, Cynata has achieved a cost-savings advantage through its unique approach to MSC manufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.

On June 22, 2016, RIKEN announced that it is resuming its retinal induced pluripotent stem cell (iPSC) study in partnership with Kyoto University.

2013 was the first time in which clinical research involving transplant of iPSCs into humans was initiated, led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan. Dr. Takahashi and her team were investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration. Although the trial was initiated in 2013 and production of iPSCs from patients began at that time, it was not until August of 2014 that the first patient, a Japanese woman, was implanted with retinal tissue generated using iPSCs derived from her own skin cells.

A team of three eye specialists, led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, implanted a 1.3 by 3.0mm sheet of iPSC-derived retinal pigment epithelium cells into the patients retina.[196] Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them. Therefore, it is major news that the RIKEN Institute will now be resuming the worlds first clinical study involving the use of iPSC-derived cells in humans.

According to the Japan Times, this attempt at the clinical study will involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency. Specifically, the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka. To learn about this announcement, view this article from Asahi Shimbun, a Tokyo- based newspaper.

In November 2015 Astellas Pharma announced it was acquiring Ocata Therapeutics for $379M. Ocata Therapeutics is a biotechnology company that specializes in the development of cellular therapies, using both adult and human embryonic stem cells to develop patient-specific therapies. The companys main laboratory and GMP facility are in Marlborough, Massachusetts, and its corporate offices are in Santa Monica, California.

When a number of private companies began to explore the possibility of using artificially re-manufactured iPSCs for therapeutic purposes, one such company that was ready to capitalize on the breakthrough technology was Ocata Therapeutics, at the time called Advanced Cell Technology. In 2010, the company announced that it had discovered several problematic issues while conducting experiments for the purpose of applying for U.S. Food and Drug Administration approval to use iPSCs in therapeutic applications. Concerns such as premature cell death, mutation into cancer cells, and low proliferation rates were some of the problems that surfaced. [17]

As a result, the company shifted its induced pluripotent stem cell approach to producing iPS cell-derived human platelets, as one of the benefits of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information. While the companys Induced Pluripotent Stem Cell-Derived Human Platelet Program received a great deal of media coverage in late 2012, including being awarded the December 2012 honor of being named one of the 10 Ideas that Will Shape the Year by New Scientist Magazine,[178]. Unfortunately, the company did not succeed in moving the concept through to clinical testing in 2013.

Nonetheless, Astellas is clearly continuing to develop Ocatas pluripotent stem cell technologies involving embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS cells). In a November 2015 presentation by Astellas President and CEO, Yoshihiko Hatanaka, he indicated that the company will aim to develop an Ophthalmic Disease Cell Therapy Franchise based around its embryonic stem cell (ESC) and induced pluripotent stem cell (iPS cell) technology. [19]

What other companies are developing iPSC derived therapeutics and products? Share your thoughts in the comments below.

BioInformant is the first and only market research firm to specialize in the stem cell industry. BioInformant research has been cited by major news outlets that include the Wall Street Journal, Nature Biotechnology, Xconomy, and Vogue Magazine. Serving Fortune 500 leaders that include GE Healthcare, Pfizer, and Goldman Sachs. BioInformant is your global leader in stem cell industry data.

Footnotes[1] CellularDynamics.com (2014). About CDI. Available at: http://www.cellulardynamics.com/about/index.html. Web. 1 Apr. 2015.[2] Ibid.[3] Takahashi K, Yamanaka S (August 2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 (4): 66376.[4] 2012 Nobel Prize in Physiology or Medicine Press Release. Nobelprize.org. Nobel Media AB 2013. Web. 7 Feb 2014. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html. Web. 1 Apr. 2015.[5] Striklin, D (Jan 13, 2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet. Retrieved Feb 1, 2014 from, http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall.%5B6%5D Striklin, D (2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet [Online]. Available at: http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. Web. 1 Apr. 2015.[7] Cellular Dynamics International (July 30, 2013). Cellular Dynamics International Announces Closing of Initial Public Offering [Press Release]. Retrieved from http://www.cellulardynamics.com/news/pr/2013_07_30.html.%5B8%5D Investors.cellulardynamics.com,. Cellular Dynamics Manufactures Cgmp HLA Superdonor Stem Cell Lines To Enable Cell Therapy With Genetic Matching (NASDAQ:ICEL). N.p., 2015. Web. 7 Mar. 2015.[9] Ibid.[10] Cellulardynamics.com,. Cellular Dynamics | Mycell Products. N.p., 2015. Web. 7 Mar. 2015.[11]Sirenko, O. et al. Multiparameter In Vitro Assessment Of Compound Effects On Cardiomyocyte Physiology Using Ipsc Cells.Journal of Biomolecular Screening 18.1 (2012): 39-53. Web. 7 Mar. 2015.[12] Sciencedirect.com,. Prevention Of -Amyloid Induced Toxicity In Human Ips Cell-Derived Neurons By Inhibition Of Cyclin-Dependent Kinases And Associated Cell Cycle Events. N.p., 2015. Web. 7 Mar. 2015.[13] Sciencedirect.com,. HER2-Targeted Liposomal Doxorubicin Displays Enhanced Anti-Tumorigenic Effects Without Associated Cardiotoxicity. N.p., 2015. Web. 7 Mar. 2015.[14] Cellular Dynamics International, Inc. Fujifilm Holdings To Acquire Cellular Dynamics International, Inc.. GlobeNewswire News Room. N.p., 2015. Web. 7 Apr. 2015.[15] Ibid.[16] Cyranoski, David. Japanese Woman Is First Recipient Of Next-Generation Stem Cells. Nature (2014): n. pag. Web. 6 Mar. 2015.[17] Advanced Cell Technologies (Feb 11, 2011). Advanced Cell and Colleagues Report Therapeutic Cells Derived From iPS Cells Display Early Aging [Press Release]. Available at: http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-and-colleagues-report-therapeutic-cells-derived-from-ips-cells-display-early-aging/.%5B18%5D Advanced Cell Technology (Dec 20, 2012). New Scientist Magazine Selects ACTs Induced Pluripotent Stem (iPS) Cell-Derived Human Platelet Program As One of 10 Ideas That Will Shape The Year [Press Release]. Available at: http://articles.latimes.com/2009/mar/06/science/sci-stemcell6. Web. 9 Apr. 2015.[19] Astellas Pharma (2015). Acquisition of Ocata Therapeutics New Step Forward in Ophthalmology with Cell Therapy Approach. Available at: https://www.astellas.com/en/corporate/news/pdf/151110_2_Eg.pdf. Web. 29 Jan. 2017.

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Market Players Developing iPS Cell Therapies - BioInformant

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The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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Quality Control and Testing

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Human Induced Pluripotent Stem Cells (HiPSC)Top:HiPSC express pluriotency markers OCT4, Nanog, LIN28 and SSEA-4.Bottom:HiPSC differentiate into cell derivatives from the 3 embryonic layers: Neuronal marker beta III tubulin (TUJ1), Smooth Muscle Actin (SMA) and Hepatocyte Nuclear Factor 3 Beta (HNF3b).

Cutting-edge development and manufacturing provides high quality, thoroughly-characterized HiPSC cells to researchers around the world. HiPSC are generated from somatic cells, eliminating ethical considerations associated with scientific work based on embryonic stem cells. Furthermore, being donor/patient-specific, they open possibilities for a wide variety of studies in biomedical research. Donor somatic cells carry the genetic makeup of the diseased patient, hence HiPSC can be used directly to model disease on a dish.

Thus, one of the main uses of HiPSC has been in genetic disease modeling in organs and tissues, such as the brain (Alzheimers, Autism Spectrum Disorders), heart (Familial Hypertrophic, Dilated, and Arrhythmogenic Right Ventricular Cardiomyopathies), and skeletal muscle (Amyotrophic Lateral Sclerosis, Spinal Muscle Atrophy). The combination of HiPSC technology and gene editing strategies such as the CRISPR/Cas9 system creates a powerful platform in which disease-causing mutations can be created on demand and sets of isogenic cell lines (with and without mutations) serve as convenient tools for disease modeling studies.

Other applications of HiPSC and iPSC-differentiated cells include drug screening, development, efficacy and toxicity assessment. As an example, through the FDA-backed CiPA (Comprehensive in vitro Pro-Arrhythmia Assessment) initiative, HiPSC-derived cardiac muscle cells (cardiomyocytes) are poised to constitute a new standard model for the evaluation of cardiotoxicity of new drugs, which is the main reason of drug withdrawal from the market. Finally, HiPSC-differentiated cells are being used in early stage technology development for applications in regenerative medicine. Bio-printing and tissue constructs have also been considered as attractive applications for HiPSC.

Human iPSC and Derived Cells are forResearch Use Only (RUO). Not for human clinical or therapeutic use.

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