An Australian-based biomedical company has been given approval from the AFL to use stem-cell therapy on players recovering from injury.

Sydney-based Regeneus has revealed it was recently given permission for its HiQCell treatment on players suffering from such issues as osteoarthritis and tendinopathy.

The treatment is banned by the World Anti-Doping Agency if it is performance-enhancing but allowed if it is solely to treat injuries.

Regeneus commercial development director Steven Barberasaid the regenerative medicine company had sought approval from the AFL for what the company says is "innovative but not experimental" treatment.

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"In 2013, Regeneus sought and received clearance from ASADA [Australian Sports Anti-Doping Authority] for its proprietary HiQCell therapy for use with athletes who participate in sporting competitions subject to the WADA Anti-Doping Code. The AFL is one of many professional sports bodies which applies the WADA Anti-Doping Code within its regulations for players," he said.

"In March this year, the AFL introduced a Prohibited Treatments List as an additional level of scrutiny over and above the WADA code for player treatments. In light of this, Regeneus made a submission to the AFL to confirm that our specific treatment is not prohibited under that list. Subsequently, the chief medical officer of the AFL has recently communicated with our primary Melbourne-based HiQCell medical practitioner that the treatment is not prohibited and can be administered on a case-by-case basis to players.

"We anticipate documented confirmation of this outcome in the near future from the AFL.

"To our knowledge, the permission is specific to HiQCell and not necessarily to cell-based therapies in general."

The AFL confirmed it had given approval on a "case-by-case" basis.

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AFL approves stem-cell therapy treatment

ROCHESTER, Minn. (KTTC) -- Medical officials are talking about a breakthrough clinical trial that could help the heart repair itself.

On Tuesday afternoon, Mayo Clinic and Cardio3 BioSciences officials outlined an FDA-approved clinical trial to be carried out in the United States. A similar trial has already been underway in Europe.

Cardio3 CEO Christian Homsy said stem cells are a major part of this heart-healing process. "What we do is take cells from a patient and we reprogram those cells to become cardiac reparative cells. Those cells have the ability to come and repair the heart." Those stem cells would come from the bone marrow of patients who suffer from heart failure.

This treatment is the result of a Mayo Clinic discovery. In Mayo's breakthrough process, stem cells that are harvested from a cardiac patient's bone marrow undergo a guided treatment designed to improve heart health in people suffering from heart failure.

Cardio3 officials said a manufacturing facility will be the first thing that is needed for this clinical trial, and the rest of the details like staffing will follow.

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Trial to use stem cells to repair heart

Ruxolitinib (trade name: Jakavi) has been approved since August 2012 for the treatment of adults with myelofibrosis. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the appropriate comparator therapy specified by the Federal Joint Committee (G-BA).

According to the results, there is an indication of considerable added benefit in comparison with "best supportive care" (BSC) because ruxolitinib is better at relieving symptoms. Moreover, a hint of an added benefit with regard to survival can be derived from the dossier. Its extent is non-quantifiable, however.

Bone marrow is replaced by connective tissue

Myelofibrosis is a rare disease of the bone marrow, in which the bone marrow is replaced by connective tissue. As a consequence of this so-called fibrosis, the bone marrow is no longer able to produce enough blood cells. Sometimes the spleen or the liver takes over some of the blood production. Then these organs enlarge and can cause abdominal discomfort and pain. The typical symptoms also include feeling of fullness, night sweats and itching. Some patients with myelofibrosis develop leukemia.

Stem cell transplantation is currently the only option to cure myelofibrosis. The drug ruxolitinib aims to relieve the symptoms of myelofibrosis.

G-BA specifies appropriate comparator therapy

Ruxolitinib is an option for patients with so-called primary or secondary myelofibrosis whose spleen is already enlarged (splenomegaly) or who have other disease-related symptoms.

The G-BA specified "best supportive care" (BSC) as appropriate comparator therapy. BSC means a therapy that provides the patient with the best possible, individually optimized, supportive treatment to alleviate symptoms and improve quality of life. This also includes adequate pain therapy.

Relevant study ongoing until 2015

In its assessment, IQWiG could include one randomized controlled trial (RCT) conducted in 89 centres in Australia, Canada and the United States (COMFORT-I). The 309 patients in total were either treated with ruxolitinib plus BSC or with placebo plus BSC.

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Ruxolitinib for myelofibrosis: Indication of considerable added benefit

By Estel Grace Masangkay

With help from the zebrafish, a team of Australian researchers has uncovered how hematopoietic stem cells (HSC) renew themselves, considered by many to be the holy grail of stem cell research.

HSCs are a significant type of stem cell present in the blood and bone marrow. These are needed for the replenishment of the bodys supply of blood and immune cells. HSCs already play a part in transplants in patients with blood cancers such as leukemia and myeloma. The stem cells are also studied for their potential to transform into vital cells including muscle, bone, and blood vessels.

Understanding how HSCs form and renew themselves has potential application in the treatment of spinal cord injuries, degenerative disorders, even diabetes. Professor Peter Currie, of the Australian Regenerative Medicine Institute at Victorias Monash University, led a research team to discover a crucial part of HSCs development. Using a high-resolution microscopy, Prof. Curies team caught HSCs on film as they formed inside zebrafish embryos. The discovery was made while the researchers were studying muscle mutations in the aquatic animal.

Zebrafish make HSCs in exactly the same way as humans do, but whats special about these guys is that their embryos and larvae develop free living and not in utero as they do in humans. So not only are these larvae free-swimming, but they are also transparent, so we could see every cell in the body forming, including HSCs, explained Prof. Currie.

While playing the film back, the researchers noticed that a buddy cell came along to help the HSCs form. Called endotome cells, they aided pre-HSCs to turn into HSCs. Prof. Currie said, Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.

The next step for the researchers is to locate the signals present in the endotome cells that trigger HSC formation in the embryo. This can help scientists make different blood cells on demand for blood-related disorders. Professor Currie also pointed out the discoverys potential for correcting genetic defects in the cell and transplanting them back in the body to treat disorders.

The teams work was published in the international journal Nature.

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Stem Cell Research Holy Grail' Uncovered, Thanks to Zebrafish

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Newswise Hematopoietic stem cells (HSCs) give rise to all other blood cell types, but their development and how their fate is determined has long remained a mystery. In a paper published online this week in Nature, researchers at the University of California, San Diego School of Medicine elaborate upon a crucial signaling pathway and the role of key proteins, which may help clear the way to generate HSCs from human pluripotent precursors, similar to advances with other kinds of tissue stem cells.

Principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine, and colleagues focused on the Notch signaling pathway, a system found in all animals and known to be critical to the generation of HSCs in vertebrates. Notch signaling between emitting and receiving cells is key to establishing HSC fate during development, said Traver. What has not been known is where, when and how Notch signal transduction is mediated.

Traver and colleagues discovered that the Notch signal is transduced into HSC precursor cells from signal emitting cells in the somite embryologic tissues that eventually contribute to development of major body structures, such as skeleton, muscle and connective tissues much earlier in the process than previously anticipated.

More specifically, they found that JAM proteins, best known for helping maintain tight junctions between endothelial cells to prevent vascular leakage, were key mediators of Notch signaling. When the researchers caused loss of function in JAM proteins in a zebrafish model, Notch signaling and HSCs were also lost. When they enforced Notch signaling through other means, HSC development was rescued.

To date, it has not been possible to generate HSCs de novo from human pluripotent precursors, like induced pluripotent stem cells, said Traver. This has been due in part to a lack of understanding of the complete set of factors that the embryo uses to make HSCs in vivo. It has also likely been due to not knowing in what order each required factor is needed.

Our studies demonstrate that Notch signaling is required much earlier than previously thought. In fact, it may be one of the earliest determinants of HSC fate. This finding strongly suggests that in vitro approaches to instruct HSC fate from induced pluripotent stem cells must focus on the Notch pathway at early time-points in the process. Our findings have also shown that JAM proteins serve as a sort of co-receptor for Notch signaling in that they are required to maintain close contact between signal-emitting and signal-receiving cells to permit strong activation of Notch in the precursors of HSCs.

The findings may have far-reaching implications for eventual development of hematopoietic stem cell-based therapies for diseases like leukemia and congenital blood disorders. Currently, it is not possible to create HSCs from differentiation of embryonic stem cells or induced pluripotent stem cells pluripotent cells artificially derived from non-pluripotent cells, such as skin cells that are being used in other therapeutic research efforts.

Co-authors include Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim and Claire Pouget, UC San Diego Department of Cellular and Molecular Medicine; Naonobu Fujita, UC San Diego Section of Cell and Developmental Biology; and Toshio Suda, Keio University, Japan.

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New Blood: Tracing the Beginnings of Hematopoietic Stem Cells

Australian scientists studying zebrafish have stumbled upon what they say is one of the most significant discoveries in stem cell research.

In research published on Thursday in the journal Nature, the Monash University scientists revealed that they uncovered how one of the most important stem cells in blood and bone marrow, the haematopoietic stem cell (HSC), is formed.

Professor Peter Currie, from Monash University's Australian Regenerative Medicine Institute, said the discovery brought researchers closer to growing HSCs in a lab.

"HSCs are the basis of bone marrow transplantations as a therapy, so when a leukaemia patient receives bone marrow, it's really these HSCs that do the heavy lifting," Professor Currie said.

"So when clinicians do bone marrow transplants, they need to find a matching donor recipients and we know that's a hit-or-miss procedure.

"So for many years people have been trying to make HSCs in the dish, and they've had very little success in doing this."

Professor Currie, who led the study, said the discovery brought scientists much closer to achieving that aim.

"It's the discovery of a completely new cell type that basically is required to give instructions to the HSC to make it become what it needs to become," he said.

"It means we now understand how HSC form in the body better, we can use that information to try to grow these cells in the dish and we hope that will lead to better treatment for people with leukaemia and blood disorders."

Professor Currie said he specialises in muscle stem cell biology and accidentally came across the discovery while studying muscle stem cells in zebrafish.

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Stem cell discovery: Australian scientists make significant find while studying zebrafish

HOT SPRINGS | A new proposal to not only save but also enhance the Veterans Affairs hospital in Hot Springs surfaced Monday, and would add not only a medical college but also a medical research component involving the use of stem cells to the facility.

The idea, put forward by an Iowa-based, non-profit corporation, would also be built around treating patients with regenerative therapy, which helps skin grow back.

Bob Krause, president of Veterans National Recover Center, was joined by surgeon Don Swift in Hot Springs to presented the proposal at a press conference Monday morning. Their multi-pronged plan has been submitted for consideration to the VA Black Hills Health Care Systems Environmental Impact Statement.

Our proposal has three main areas, Krause told the small audience that attended the press conference. First, the creation of Battle Mountain College, for the training of doctors in the discipline of osteopathic medicine. Krause noted that by having the additional training, a major first hurdle in the BHHCS proposal to close the Hot Springsan inability to draw doctors to the area would be addressed.

We would also build the Battle Mountain Research Institute, for further research into the regenerative therapies, along with the Battle Mountain Clinic to treat those veterans and others who require this cutting-edge treatment, Krause said.

He added that the proposal stipulated that it is to be considered in its entirety and that if the VA medical center should close, everything is off the table. This proposal is not mutually exclusive of the one presented by Save the VA, he said of the Hot Springs-area group that is fighting to save the hospital from closure by the federal government.

Krause and Swift said that the technology, which was created in Switzerland by the military and is awaiting FDA approval in the United States, utilizes regenerative or restorative cells created from fetal stem cells to jump-start a patients ability to regenerate skin tissue. After the patients own skin begins to grow, the regenerative cells die, Krause said.

He said that submitting the new proposal through the EIS process was important, since the research would need to be conducted on federal property because South Dakota law does not allow stem cell research at this time.

Swift noted that an important part to the regenerative therapy process was access to mineral water to help hydrate the tissue and fight infection. Such water can be found in Hot Springs.

In response to a question, Krause said that he understands that there is a question involving fetal stem cell research. But what is the greater good? he asked. Do we overlook a veteran who has experienced having all of his skin burned away by an [explosion], instead of developing that single cell that could help? Are you going to walk away from that cell?

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New idea for VA would bring an educational focus

(PRWEB UK) 11 August 2014

BioEden the specialist tooth stem cell bank calls for a more intelligent approach, transparency and public education regarding stem cell banking.

"The public needs to be made aware that the success of stem cell medicine is largely dependant on the right material being available at the right time," says Tony Veverka Group CEO of the rapidly expanding specialist bank.

"With 1 in 3 people predicted to use stem cell therapy within their lifetime people need to know what their choices are at a time when they are able to do something about it, for example obtaining stem cells from their childrens naturally shed baby teeth."

BioEden pioneered the banking of stem cells from childrens baby teeth in 2006 in Austin Texas, and now operates in 21 countries.

BioEden says its unique process has many advantages over other forms and sources of stem cells, and eliminates the costly and painful process of getting stem cells from bone marrow for example.

The BioEden process is patent protected and offers the most natural form of stem cell banking that exists today.

"It is nonsense to say that a dental surgeon needs to extract a childs baby tooth in order to get the best result. The tooth falls out naturally and providing the stem cell bank offers quality transportation and processing, not even dental intervention is required," says Mr Veverka.

There are significant advantages in banking stem cells from teeth over cord blood for example, including the potential for a much wider therapeutic application, its non-invasive, not limited to the number of cells such as with cord blood during the birthing process, and is the least expensive form of private banking there is.

Banking your child's cells is the only way of ensuring a perfect stem cell match, eliminating the emotional distress caused when no match can be found.

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BioEden calls for transparancy and education on stem cell availability

(PRWEB UK) 9 August 2014

Stem cell therapy and treatments continue to move on in finding cures for diseases that in the past were thought to be incurable. The success of stem cell treatment and therapy relies to a great extent on the ability for the patient to have a stem cell match. Although stem cell banking has been available for a number of years, the cost for many has been a barrier.

Specialist stem cell bank BioEden who operate in 21 countries have come up with a solution that brings this potentially life saving opportunity within an affordable range for the majority.

Their aim is to make stem cell therapy an affordable reality and hope that their new approach which includes a low monthly membership option will do just that.

As more and more people bank their children's stem cells for their future use, the problem of finding a stem cell match could become a thing of the past.

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Due to a radical new approach by stem cell bank BioEden future generations could be guaranteed a stem cell match

By Amy Norton HealthDay Reporter

THURSDAY, Aug. 7, 2014 (HealthDay News) -- In a step toward using stem cells to treat paralysis, scientists were able to use cells from an elderly man's skin to regrow nerve connections in rats with damaged spinal cords.

Reporting in the Aug. 7 online issue of Neuron, researchers say the human stem cells triggered the growth of numerous axons -- the fibers that extend from the body of a neuron (nerve cell) to send electrical impulses to other cells.

Some axons even reached the animals' brains, according to the team led by Dr. Mark Tuszynski, a professor of neurosciences at the University of California, San Diego.

"This degree of growth in axons has not been appreciated before," Tuszynski said. But he cautioned that there is still much to be learned about how the new nerve fibers behave in laboratory animals.

Tuszynski likened the potential for stem-cell-induced axon growth to nuclear fusion. If it's contained, you get energy; if it's not contained, you get an explosion.

"Too much axon growth into the wrong places would be a bad thing," Tuszynski said.

For years, researchers have studied the potential for stem cells to restore functioning nerve connections in people with spinal cord injuries. Stem cells are primitive cells that have the capacity to develop into various types of body tissue. Stem cells can come from embryos or be generated from cells taken from a person.

For their study, Tuszynski's team used so-called induced pluripotent stem cells. They took skin cells from a healthy 86-year-old man and genetically reprogrammed them to become similar to embryonic stem cells.

Those stem cells were then used to create primitive neurons, which the researchers embedded into a special scaffold created with the help of proteins called growth factors. From there, the human neurons were grafted into lab rats with spinal cord injuries.

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Scientists Inch Closer Toward Using Stem Cells for Spinal Injuries

Building upon previous research, scientists at the University of California, San Diego School of Medicine and Veteran's Affairs San Diego Healthcare System report that neurons derived from human induced pluripotent stem cells (iPSC) and grafted into rats after a spinal cord injury produced cells with tens of thousands of axons extending virtually the entire length of the animals' central nervous system.

Writing in the August 7 early online edition of Neuron, lead scientist Paul Lu, PhD, of the UC San Diego Department of Neurosciences and colleagues said the human iPSC-derived axons extended through the white matter of the injury sites, frequently penetrating adjacent gray matter to form synapses with rat neurons. Similarly, rat motor axons pierced the human iPSC grafts to form their own synapses.

The iPSCs used were developed from a healthy 86-year-old human male.

"These findings indicate that intrinsic neuronal mechanisms readily overcome the barriers created by a spinal cord injury to extend many axons over very long distances, and that these capabilities persist even in neurons reprogrammed from very aged human cells," said senior author Mark Tuszynski, MD, PhD, professor of Neurosciences and director of the UC San Diego Center for Neural Repair.

For several years, Tuszynski and colleagues have been steadily chipping away at the notion that a spinal cord injury necessarily results in permanent dysfunction and paralysis. Earlier work has shown that grafted stem cells reprogrammed to become neurons can, in fact, form new, functional circuits across an injury site, with the treated animals experiencing some restored ability to move affected limbs. The new findings underscore the potential of iPSC-based therapy and suggest a host of new studies and questions to be asked, such as whether axons can be guided and how will they develop, function and mature over longer periods of time.

While neural stem cell therapies are already advancing to clinical trials, this research raises cautionary notes about moving to human therapy too quickly, said Tuszynski.

"The enormous outgrowth of axons to many regions of the spinal cord and even deeply into the brain raises questions of possible harmful side effects if axons are mistargeted. We also need to learn if the new connections formed by axons are stable over time, and if implanted human neural stem cells are maturing on a human time frame -- months to years -- or more rapidly. If maturity is reached on a human time frame, it could take months to years to observe functional benefits or problems in human clinical trials."

In the latest work, Lu, Tuszynski and colleagues converted skin cells from a healthy 86-year-old man into iPSCs, which possess the ability to become almost any kind of cell. The iPSCs were then reprogrammed to become neurons in collaboration with the laboratory of Larry Goldstein, PhD, director of the UC San Diego Sanford Stem Cell Clinical Center. The new human neurons were subsequently embedded in a matrix containing growth factors and grafted into two-week-old spinal cord injuries in rats.

Three months later, researchers examined the post-transplantation injury sites. They found biomarkers indicating the presence of mature neurons and extensive axonal growth across long distances in the rats' spinal cords, even extending into the brain. The axons traversed wound tissues to penetrate and connect with existing rat neurons. Similarly, rat neurons extended axons into the grafted material and cells. The transplants produced no detectable tumors.

While numerous connections were formed between the implanted human cells and rat cells, functional recovery was not found. However, Lu noted that tests assessed the rats' skilled use of the hand. Simpler assays of leg movement could still show benefit. Also, several iPSC grafts contained scars that may have blocked beneficial effects of new connections. Continuing research seeks to optimize transplantation methods to eliminate scar formation.

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Dramatic growth of grafted stem cells in rat spinal cord

A method of growing human cells from tissue removed from a patient's gastrointestinal (GI) tract eventually may help scientists develop tailor-made therapies for inflammatory bowel disease and other GI conditions.

Reporting online recently in the journal Gut, researchers at Washington University School of Medicine in St. Louis said they have made cell lines from individual patients in as little as two weeks. They have created more than 65 such cell lines using tissue from 47 patients who had routine endoscopic screening procedures, such as colonoscopies. A cell line is a population of cells in culture with the same genetic makeup.

The scientists said the cell lines can help them understand the underlying problems in the GI tracts of individual patients and be used to test new treatments.

"While it has been technically possible to isolate intestinal epithelial stem cells from patients, it has been challenging to use the material in ways that would benefit them on an individual basis," said co-senior investigator Thaddeus S. Stappenbeck, MD, PhD, a professor of pathology and immunology. "This study advances the field in that we have developed new methods that allow for the rapid expansion of intestinal epithelial stem cells in culture. That breaks a bottleneck and allows us to develop new ways to test drug and environmental interactions in specific patients."

To grow the human cells, the researchers adapted a system used to grow intestinal epithelial stem cells in mice. In the GI tract, epithelial cells line the inner surface of the esophagus, stomach and intestines.

"An additional important feature of this system is that we can isolate stem cell lines from intestinal biopsies," said first author Kelli L. VanDussen, PhD, a postdoctoral fellow in Stappenbeck's laboratory. "These biopsies are very small tissue fragments that are routinely collected by a gastroenterologist during endoscopy procedures. We have refined this technique, so we have nearly 100 percent success in creating cell lines from individual patient biopsies."

The researchers developed an experimental system that created high levels of critical factors to isolate and expand intestinal epithelial stem cells, including a signaling protein called Wnt and a related protein called R-spondin, which enhances the Wnt signal. They also exposed the cells to a protein called Noggin, which prevented the cells from differentiating into other cell types that live in the GI tract.

After growing the intestinal cell lines, the investigators collaborated with Phillip I. Tarr, MD, the Melvin E. Carnahan Professor of Pediatrics and director of the Division of Pediatric Gastroenterology and Nutrition, to conduct experiments and see how the cells interacted with bacterial pathogens like E. coli.

This showed that pathogenic strains of E. coli attached to intestinal epithelial cells. That attachment is thought to be the critical step in stimulating disease. The investigators said the experimental system they created should lead to new methods to uncover therapies for treating bacterial infections of the intestine.

"In the past, the only really robust method for studying GI epithelial cells was to use cancer cell lines," said co-senior investigator Matthew A. Ciorba, MD, a gastroenterologist and assistant professor of medicine. "However, cancer cells behave differently than the noncancerous GI epithelium, which is affected in patients with conditions such as inflammatory bowel disease. This technique now allows us to study cells identical to the ones that live in a patient's GI tract. Plus, we can grow the cell lines quickly enough that it should be possible to develop a personalized approach to understanding a patient's disease and to tailor treatment based on a patient's underlying problem."

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Growing human GI cells may lead to personalized treatments

Yoshiki Sasai, who was embroiled in a stem-cell scandal, committed suicide He was found with a rope around his neck at science institute Riken in Japan Mr Sasai, 52, was deputy chief of Riken's Center for Developmental Biology He co-authored stem-cell research papers with falsified contents

By Ted Thornhill

Published: 06:20 EST, 5 August 2014 | Updated: 13:25 EST, 5 August 2014

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A senior Japanese scientist embroiled in a stem-cell research scandal died on Tuesday in an apparent suicide, police said.

Yoshiki Sasai, who supervised and co-authored stem-cell research papers that had to be retracted due to falsified contents, was found suffering from cardiac arrest at the government-affiliated science institute Riken in Kobe, in western Japan, according to Hyogo prefectural police.

Sasai, 52, was deputy chief of Riken's Center for Developmental Biology.

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Japanese scientist stem-cell scientist Yoshiki Sasai commits suicide

Brain cells that were grafted into the brains of mice have become fully functionally integrated after six months. The successful neuron transplant could pave the way for therapies to treat neurodegenerative diseases such as Parkinson's.

A team of stem cell researchers at the Luxembourg Centre for Systems Biomedicine created the grafted neurons -- induced neuronal stem cells -- in a petri dish out of the host's reprogrammed skin cells. This technique dramatically improved the compatibility of the implanted cells.

Six months after the brain cells were implanted into the hippocampus and cortex regions of the brain, the neurons were fully integrated with the original brain cells via newly formed synapses (the contact points between neurons). The induced neuronal stem cells had changed into different types of brain cells -- neurons, astrocytes and oligodendrocytes -- over time within the host brain. Functional integration with the existing network of cells is absolutely critical for long-term survival of the new brain tissue. The new brain cells exhibited normal activity in tests and the mice showed no adverse side effects.

The plan for researchers is now to explore replacing the type of neurons that tend to die off in the brain of Parkinson's patients -- those neurons found in the substantia nigra that produce dopamine. It may, in the future, be possible to implant neurons to produce the diminished dopamine, which could prove to be an effective treatment for the disease.

Of course, it's a bit leap from the current research to human trials. "Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future," says team leader and stem cell researcher Jens Schwamborn. "Our research results have taken us a step further in this direction."

The study has been published in Stem Cell Reports and is available to read for free.

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Implanted brain cells integrate fully with mouse brain tissue

Abstract

Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair.

Keywords: Stem cell, Regeneration, Heart, Cardiomyocytes

Repairing the injured body with its own tissue as a substrate has captured human fascination for a long time. In Greek mythology, the Lernaean Hydra was a serpent-like creature with multiple heads that regenerated each time they were cut off and Prometheus, a titan punished by Zeus for stealing fire, had a liver that was able to regenerate each night after it was eaten by an eagle. In 1740, Abraham Tembley discovered that microscopic, freshwater animals had the ability to regenerate their head after amputation, later followed by others who discovered that amphibians have the ability to regenerate their tails, limbs, jaws, and eyes.[1],[2] It took scientists until 1933 before they discovered that some human organs, such as the liver, also have the ability to regenerate.[3]

Regenerative therapies are of major interest in cardiovascular medicine. Most cardiovascular diseases, including ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes and in other diseases, such as sick sinus syndrome, specific cardiac cell properties are missing. Unlike the Lernaean Hydra or the human liver, the heart does not have the ability to regenerate itself spontaneously once damaged. Cardiomyocytes are terminally differentiated and have a limited proliferative capacity. Lost cardiomyocytes are replaced by fibroblasts and connective tissue with the remaining cardiomyocytes becoming hypertrophic, which may eventually lead to heart failure. On the contrary, stem cells proliferate indefinitely and can be directed to differentiate into specialized cell types such as cardiomyocytes. The goal of stem cell-based regenerative medicine in cardiovascular disease, therefore, is to create healthy, functional cardiac cells that are able to integrate in the injured heart and restore its function.

In the past decades, several stem cell types have been discovered. These stem cells can be subdivided based on their differentiation capacity. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are able to differentiate into all three embryonic germ layers, whereas multipotent stem cells can differentiate into a number of closely related cell types of a single embryonic germ layer. Cardiomyocytes were derived from several stem cell sources (). Other types of stem cells do not differentiate into cardiomyocytes themselves, but support cardiac repair by different mechanisms (). In this review, we will refer to all stem cell-derived cardiomyocytes and differentiated cell types enriched for cardiomyocytes as stem cell-derived cardiomyocytes (SCD-CMs), while we will refer to non-cardiomyocyte derivatives (such as vascular cells) as stem cell-derived cardiac support cells (SCD-CSCs).

Summary of stem cells used for cardiac repair.

Characteristics of stem cells studied for cardiac regeneration potential.

In this review, we will give an introduction to the principles of stem cell-based cardiac repair. Our aim is to give a concise up-to date overview of the therapeutic possibilities of stem cells for cardiac injury. First, we describe general requirements for stem cell therapy. After that, we will discuss in more detail the different stem cell sources and their therapeutic effects, since these vary for each cell type.

In order to be suitable for cardiac repair, stem cell-derived cardiac cells should resemble the original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Ideally there would also be beneficial effects on the host myocardium, for example, by stimulating proliferation or differentiation of local progenitors, neovascularization or by inhibiting apoptosis. The minimum requirement for the donor cells is to have no adverse effects. Finally, stem cell therapy needs to be safe, reproducible, and affordable. Each of these requirements will be discussed separately. ()

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Stem cells for cardiac repair: an introduction

By Sidhartha Banerjee, The Canadian Press Published Saturday, August 2, 2014 8:56AM EDT

MONTREAL -- A Quebec woman's desperate online plea for a compatible stem-cell donor in her bid to fight cancer a second time is shedding light on the lack of minorities on official lists in Canada and abroad.

Mai Duong finds herself battling leukemia again and doctors say they would like to proceed with a transplant of bone marrow or cord blood stem cells within a month.

But Duong, 34, has discovered that locating the right person can be a needle-in-a-haystack challenge, particularly for those who are from a non-Caucasian background.

"This is a global problem," Duong, who is of Vietnamese origin, said in an interview from her room at Montreal's Maisonneuve-Rosemont Hospital.

"We can't do a scavenger hunt every time someone has this type of problem."

Duong, who returned home a few days after being interviewed, said a recent bone marrow biopsy showed no signs of cancer. She will now begin four weeks of maintenance chemotherapy, which is given in lower doses to assist in prolonging a remission.

The mother of a four-year-old girl, Duong successfully fought off acute leukemia in 2013 with chemotherapy. She had to terminate a 15-week pregnancy to undergo the treatment. Duong was in remission until a blood test revealed leukemia had returned this past May.

"Seventy per cent of people who had that type of leukemia were just cured with chemotherapy and unfortunately I'm in the 30 per cent," she said.

The diagnosis and a lack of a match in her family has touched off a mad scramble to find a fellow Vietnamese donor. An online campaign has taken that hunt global.

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Cancer fight shows lack of minorities on donor lists

Boston, MA (PRWEB) July 31, 2014

Bostons Adult Stem Cell Technology Center, LLC (ASCTC) finds itself flush with innovative adult stem cell biotechnologies. Currently the company holds seven recently issued patents and has three additional patent applications currently under examination by the U.S. Patent and Trademarks Office.

The patented inventions address two of the most vexing problems in adult stem cell biology research and regenerative medicine. Adult stem cells are difficult to identify; and they have been difficult to multiply to sufficient numbers to support regenerative medicine applications.

ASCTC has addressed the identity problem by developing patented biomarkers that are found exclusively on adult stem cells. The biomarkers are based on ASCTCs expertise in defining properties of adult stem cells that are not shared by any other normal cell types in the body. The patented biomarkers also identify some types of cancer stem cells. Therefore, they have applications in both stem cell medicine and cancer medicine.

ASCTCa success in developing procedures for producing adult stem cells in large numbers is due to the companys expertise in adult stem cell growth control. ASCTCs technology uses natural compounds found in the body to instruct adult stem cells to multiply in a controlled manner as during normal body growth.

The companys patented method for controlling adult stem cells to multiply without losing their stem cell properties has applications for many different types of adult stem cells. ASCTCs approved patents demonstrate the application of the method for production of human liver stem cells, hair follicle stem cells, and human pancreatic stem cells; but the technology has general application to adult stem cells found in many other types of organs and tissues.

In addition to the main focus on adult stem cell technologies, ASCTCs most recently issued patent applies its cell multiplication methods to produce induced pluripotent stem cells (iPSCs) without transferring exogenous genes. This gene-free single agent method should offer significant value to the many mushrooming companies that supply iPSCs and iPSC production reagents.

As a small start-up, ASCTC is employing a social media marketing strategy. In the past week, the company has launched patent licensing ads on LinkedIn, Vocus, and Facebook, as well increased its advertising references within its recently established Twitter presence.

It would be a shame for these technologies to lie dormant, just because our hands are full with other projects at the moment. James Sherley, director of ASCTC, relates that the companys two main business efforts require only a fraction of its available intellectual property. ASCTC is currently focused on bringing laboratory-scale production of human liver stem cells to manufacturing scales and developing a computer simulation assay for preclinical detection of drug candidates with intolerable toxicity due to adverse effects on adult stem cells.

Sherley adds, We already have a few companies that have expressed interest in licensing. But we could do a lot better at reaching others whose development efforts would benefit from ASCTCs unique technologies. Love to hear from ViaCyte!

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The Adult Stem Cell Technology Center, LLC Launches A Marketing Campaign To License Adult Stem Cell Biotechnologies

"Bubble boy" David Vetter lived in a protective environment designed by NASA engineers. He died of complications after receiving a bone marrow transplant in 1984, at the age of 12. Baylor College of Medicine Photo Archives

Babies born with so-called "bubble boy" disease can often be cured with a stem cell transplant, regardless of the donor -- but early treatment is critical, a new study finds.

Severe combined immunodeficiency (SCID), as the condition is medically known, actually refers to a group of rare genetic disorders that all but eliminate the immune system. That leaves children at high risk of severe infections.

The term "bubble boy" became popular after a Texas boy with SCID lived in a plastic bubble to ward off infections. The boy, David Vetter, died in 1984 at the age of 12, after an unsuccessful bone marrow transplant -- an attempt to give him a functioning immune system.

15 Photos

Immune disorder forced David Vetter to live in bubble - but breakthroughs from his story now enable similar kids to live free

In the best-case scenario, a child would get stem cells -- the blood-forming cells within bone marrow -- from a sibling who is a perfect match for certain immune-system genes.

But that's not always an option, partly because kids with SCID are often their parents' first child, said Dr. John Cunningham, director of hematopoietic stem cell transplantation at the University of Chicago Comer Children's Hospital. He was not involved in the study.

In those cases, doctors typically turn to a parent -- who is usually a "half" match, but whose stem cells can be purified to improve the odds of success. Sometimes, stem cells from an unrelated, genetically matched donor can be used.

The good news: Regardless of the donor, children with SCID can frequently be cured, according to the new findings. But early detection and treatment is vital.

Original post:
Early stem cell transplant may cure "bubble boy" disease

When Karen Mitchell read the popular blog written by teenage terminal cancer sufferer Alice Pyne, not only was she deeply moved but also inspired.

Pride Of Britain winner Alice, who had Hodgkins lymphoma from the age of 12, took to social media to urge people to join the bone marrow register. Karen decided she too would sign up to donate her stem cells and save lives.

But there was one thing holding her back her weight.

She was 25st and had a BMI of 60, well above the healthy range of 18-25, and when she began the online registration for Anthony Nolan with her weight and height 5ft 6in she was rejected as being too fat.

So, instead she sent brave Alice a tweet, promising she would lose weight to join the register. And when Alice replied, urging her not to give up, Karen swore that she would not fail.

Now shes lost an incredible 11st 7lb and next week she will make a life-saving donation in memory of Alice, who died in January 2013.

Alice told me not to give up and I didnt want to let her down, says Karen. Her amazing legacy can go on saving lives and I hope everyone reading this will donate as well not for me but for Alice.

Karen, from Great Yarmouth, Norfolk, had battled with her weight for as long as she could remember. Her teenage years were a misery as she was forced to dress in size 18 clothes. Even turning vegetarian and making her staple food cheese at 15 didnt help solve her weight problem.

I longed to wear trendy clothes like the other girls at my school but I could only shop in the fat section of shops, she says.

Karen married when she was 27 but says she knew when she walked down the aisle in her size 28 wedding dress that the marriage was already doomed.

Link:
'I promised brave cancer teenager Alice I'd lose 11st so I could donate bone marrow'

6 hours ago Induced pluripotent stem cellsknown as iPS cells, and which act very much like embryonic stem cellsare here growing into heart cells (blue) and nerve cells (green). Credit: Gladstone Institutes/Chris Goodfellow

A new stem-cell discovery might one day lead to a more streamlined process for obtaining stem cells, which in turn could be used in the development of replacement tissue for failing body parts, according to UC San Francisco scientists who reported the findings in the current edition of Cell.

The work builds on a strategy that involves reprogramming adult cells back to an embryonic state in which they again have the potential to become any type of cell.

The efficiency of this process may soon increase thanks to the scientists' identification of biochemical pathways that can inhibit the necessary reprogramming of gene activity in adult human cells. Removing these barriers increased the efficiency of stem-cell production, the researchers found.

"Our new work has important implications for both regenerative medicine and cancer research," said Miguel Ramalho-Santos, PhD, associate professor of obstetrics, gynecology and reproductive sciences and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, who led the research, funded in part by a prestigious NIH Director's New Innovator Award.

The earlier discovery that it was possible to take specialized adult cells and reverse the developmental clock to strip the mature cells of their distinctive identities and characteristics and to make them immortal, reprogrammable cells that theoretically can be used to replace any tissue type led to a share of the Nobel Prize in Physiology or Medicine being awarded to UCSF, Gladstone Institutes and Kyoto University researcher Shinya Yamanaka, MD, in 2012.

Turning Back the Clock on Cellular Maturation

These induced pluripotent stem (iPS) cells are regarded as an alternative experimental approach to ongoing efforts to develop tissue from stem cells obtained from early-stage human embryos. However, despite the promise of iPS cells and the excitement surrounding iPS research, the percentage of adult cells successfully converted to iPS cells is typically low, and the resultant cells often retain traces of their earlier lives as specialized cells.

Researchers generate stem cells by forcing the activation within adult cells of pluripotency-inducing genesstarting with the so-called "Yamanaka factors" a process that turns back the clock on cellular maturation.

Yet, as Ramalho-Santos notes, "From the time of the discovery of iPS cells, it was appreciated that the specialized cells from which they are derived are not a blank slate. They express their own genes that may resist or counter reprogramming."

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Stem cell advance may increase efficiency of tissue regeneration