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Artificial embryonic stem cells have quality problems: study

By Dr. Matthew Watson

Salk Institute scientist Joseph Ecker holds a flow cell slide used in a genome sequencing machine. Ecker and colleagues compared the genomes of two kinds of artificial embryonic stem cells for a study comparing their quality.

In a setback for hopes of therapy with a promising kind of artificial embryonic stem cells, a study published in the journal Nature has found that these "induced pluripotent stem cells" have serious quality issues.

However, scientists who performed the study, including researchers from the Salk Institute and UC San Diego, say it should be possible to improve the quality of these IPS cells. They say lessons can be learned from studying a newer technique of making human embryonic stem cells through nuclear transfer, the same technology used to create Dolly the cloned sheep.

In addition, the study does not prove that the quality problems will affect therapy with the cells, said scientists who examined the study. That remains to be tested.

The IPS cells are made from skin cells treated with "reprogramming" factors that turn back the clock, so they very closely resemble embryonic stem cells. The hope is that these IPS cells could be differentiated into cells that can repair injuries or relieve diseases. Because they can be made from a patient's own cells, the cells are genetically matched, reducing worries of immune rejection.

In San Diego, scientists led by Jeanne Loring at The Scripps Research Institute have created IPS cells from the skin cells of Parkinson's disease patients, and turned the IPS cells into neurons that produce dopamine. They hope to get approval next year to implant these cells into the patients, relieving symptoms for many years. The project is online under the name Summit4StemCell.org.

A major concern is that IPS cells display abnormal patterns of gene activation and repression. This is controlled by a process called methylation. This process adds chemicals called methyl groups to DNA, but these "epigenetic" changes do not change the underlying DNA sequence. Methylation represses gene function; removing the methyl groups, or demethylation, activates them.

The Nature study was led by Shoukhrat Mitalipov of Oregon Health & Scence University. Mitalipov made headlines last year for applying nuclear transfer to derive human embryonic stem cells, the first time this has been achieved in human cells. These cells can be made to be a near-perfect genetic match to the patient, and their quality closely resembles those of true embryonic stem cells.

"We know that the embryonic stem cells are the gold standard, and we've been always trying to make patient-matched cells that would match the gold standard," Mitalipov said. "And at this point it looks like the NT (nuclear transfer) cells produce exactly those cells that would be best."

Nuclear transfer involves placing a nucleus from a skin cell into an egg cell that has had its nucleus removed. The cell is then stimulated, and starts dividing in the same way a fertilized egg cell divides to form an embryo.

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Nuclear Transfer Proven An Effective Method In Stem Cell Production

By Dr. Matthew Watson

July 3, 2014

redOrbit Staff & Wire Reports Your Universe Online

A new process known as somatic cell nuclear transfer is far better and much more accurate when it comes to coaxing embryonic stem cells out of human skin tissue, according to new research appearing in Tuesdays edition of the journal Nature.

Scientists from Oregon Health & Science University (OHSU), the University of California-San Diego (UCSD) School of Medicine and the Salk Institute for Biological Studies created stem cells using two different methods: nuclear transfer, which involves moving genetic material from a skin cell into an empty egg cell, and a more traditional method in which activating a small number of genes reverts adults cells back to an embryonic state.

Experts believe that stem cell therapies could someday be used to replace human cells damaged through injury or illness, including spinal cord injuries, diabetes, Parkinsons disease and multiple sclerosis. Human embryonic stem cells (ES cells), which are cells cultured from discarded embryos, are viewed by scientists as the gold standard of the field, and the new study reports that somatic cell nuclear transfer (SCNT) more closely resembled ES cells.

This marks the first time that researchers had directly compared the SCNT method with the induced pluripotent stem cell (iPS cell) technique, and in a statement, co-senior author and UCSD assistant professor in reproductive medicine Dr. Louise Laurent explained that the nuclear transfer ES cells were more completely reprogrammed and had fewer alterations in gene expression and DNA methylation levels than the iPS cells.

Access to actual human embryonic stem cells (hESCs) has been limited in the US due to ethical and logistical issues, forcing researchers to devise other methods to create stem cells, the study authors explained. Typically, that means creating iPS cells by taking adult cells and adding in a mixture of genes that regress those cells to a pluripotent stem-cell state. Those cells can then be coaxed into cells resembling those found in the heart or brain.

Over the past year, however, an OHSU-led team of researchers have built upon somatic cell nuclear transfer (the same technique used for cloning organisms) to transplant the DNA-containing nucleus of a skin cell into an empty human egg. Once completed, the combination naturally matures into a group of stem cells.

For the first time, the OHSU, UCSD and Salk Institute researchers conducted a direct, in-depth comparison of the two different methods. They created four nuclear transfer ES cell lines and seven iPS cell lines using the same skin cells as the donor genetic material source, and then compared them to a pair of standard human ES lines.

A battery of standard tests revealed that all 13 cell lines were shown to be pluripotent. However, when the researchers used powerful genomic techniques to take a closer look at the DNA methylation (a biochemical process responsible for turning genes on or off) and the gene expression signatures of each cell line, they discovered that the nuclear transfer ES cells more closely resembled those of ES cells than did iPS cells in both characteristics.

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Bone marrow transplants can reverse adult sickle cell disease

By Dr. Matthew Watson

This image provided by the National Institutes of Health shows red blood cells in a patient with sickle cell disease at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

This image provided by the National Institutes of Health shows red blood cells in a different sickle cell patient, after a bone marrow transplant at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results seen with a similar technique used in children.

The researchers and others say the findings show age need not be a barrier and that the technique may change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were even able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening; patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, with hopes that the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

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Her own stem cells saved her from hip replacement

By Dr. Matthew Watson

Apollo Health City team did autologous stem cell procedure to save both the hip joints

Hyderabad, June 30:

A team of doctors from a city hospital have harvested stem cells of a person using bone morrow from the pelvis area to replace some dead tissues in the hip. In this process, they saved the patient from undergoing a hip replacement.

The Apollo Health City team, headed by orthopaedic specialist Paripati Sharat Kumar, diagnosed a 39-year-old woman to be suffering from Avascular Necrosis, making her writhe with pain in her two hip joints. Her condition would require undergoing a replacement of hips.

After assessing her condition, the team has decided to go for autologous stem cell procedure (where donor and the receiver is the same person) to save both the hip joints.

The minimally invasive procedure involved taking bone marrow aspirate from the patients pelvis. Stem cells were harvested from the aspirate, through a process that takes about 15 minutes. Stems cells were planted in the area of damage under fluoroscopy control following core decompression, Sharat Kumar said here in a statementon Monday.

He felt that autologous stem cell treatments could edge out joint replacement procedures to a large extent in days to come. The scope of this procedure in orthopaedics and sports medicine is enormous. This could be extended to indications include osteoarthritis of knee, shoulder, hip, elbows, ankle and spine, he said.

(This article was published on June 30, 2014)

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New Stem Cell Production Method Could Clear Way for Anticancer Gene Therapy

By Dr. Matthew Watson

Durham, NC (PRWEB) June 27, 2014

A new study released today in STEM CELLS Translational Medicine suggests a new way to produce endothelial progenitor cells in quantities large enough to be feasible for use in developing new cancer treatments.

Endothelial progenitor cells (EPCs) are rare stem cells that circulate in the blood with the ability to differentiate into the cells that make up the lining of blood vessels. With an intrinsic ability to home to tumors, researchers have focused on them as a way to deliver gene therapy straight to the cancer. However, the challenge has been to collect enough EPCs for this use.

This new study, by researchers at the Institute of Bioengineering and Nanotechnology, National University of Singapore and Zhejiang University led by Shu Wang, Ph.D., explored whether human induced pluripotent stem cells (iPSCs) could provide the answer. iPSCs, generated from adult cells, can propagate indefinitely and give rise to every other cell type in the body, much like human embryonic stem cells, which are considered the gold standard for stem cell therapy.

However, human iPS cells can be generated relatively easily through reprogramming, a procedure that circumvents the bioethical controversies associated with deriving embryonic stem cells from human embryos, Dr. Wang said.

After inducing human iPS cells to differentiate into the EPCs, the research team compared the stability and reliability of the induced EPCs with regular EPCs by injecting them into mice with breast cancer that had metastasized (traveled) to the lungs. The results showed that their induced EPCs retained the intrinsic ability to home to tumors, just as regular EPCs do. They also did not promote tumor growth or metastasis.

We next tested the induced EPCs therapeutic potential by infusing them with an anticancer gene and injecting them into the mice, Dr. Wang said. The results indicated that the tumors were reduced and the animals survival rates increased.

Since this approach may use patient's own cells to prepare cellular therapeutics and is based on non-toxic immunotherapy, it holds potential for translation to clinical application and may be particularly valuable as a new type of anti-metastatic cancer therapy.

With the increasing potential of using EPCs as cancer therapeutics, it is important to have a reliable and stable supply of human EPCs, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. This study demonstrates the feasibility of generating EPs from early-passage human iPS cells.

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Cell scientists slow degeneration in motor neuron mice

By Dr. Matthew Watson

TOKYO: Japanese stem cell scientists have succeeded in slowing the deterioration of mice with motor neuron disease, possibly paving the way for eventual human treatment, according to a new paper.

A team of researchers from the Kyoto University and Keio University transplanted specially created cells into mice with amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's, or motor neuron disease.

The progress of the creatures' neurological degeneration was slowed by almost eight per cent, according to the paper, which was published on Thursday in the scholarly journal Stem Cell Reports.

ALS is a disorder of motor neurons -- nerves that control movement -- leading to the loss of the ability to control muscles and their eventual atrophy.

While it frequently has no effect on cognitive function, it progresses to affect most of the muscles in the body, including those used to eat and breathe.

British theoretical physicist Stephen Hawking has been almost completely paralysed by the condition.

In their study, the Japanese team used human "iPS" -- induced pluripotent stem cells, building-block cells akin to those found in embryos, which have the potential to turn into any cell in the body.

From the iPS cells they created special progenitor cells and transplanted them into the lumbar spinal cord of ALS mice.

Animals that had been implanted lived 7.8 per cent longer than the control group without the procedure, the paper said.

"The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs (human induced pluripotent stem cells) as cell source," the team said in the paper.

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Designer T cells fight viruses after transplants – Quincy Herald-Whig | Illinois & Missouri News, Sports

By Dr. Matthew Watson

By LAURAN NEERGAARD AP Medical Writer

WASHINGTON (AP) - Bone marrow transplants save thousands of lives but patients are vulnerable to severe viral infections in the months afterward, until their new immune system kicks in. Now scientists are developing protection for that risky period - injections of cells specially designed to fend off up to five different viruses at once.

"These viruses are a huge problem, and there's a huge need for these products," said Dr. Ann Leen, who leads a team at Baylor College of Medicine and Texas Children's Hospital that found an easier way to produce these long-desired designer T cells.

Healthy people have an army of T cells that roams the body, primed to recognize and fight viruses. People with suppressed immune systems - such as those undergoing a bone marrow transplant to treat leukemia or other diseases - lack that protection. It can take anywhere from four months to more than a year for marrow stem cells from a healthy donor to take root and start producing new immune cells for the recipient. When patients get sick before then, today's antiviral medications don't always work and cause lots of side effects.

The proposed solution: Take certain virus-fighting T cells from that same bone marrow donor, and freeze them to use if the recipient gets sick. Years of experiments show it can work. But turning the idea into an easy-to-use treatment has been difficult. A dose had to be customized to each donor-recipient pair and protected against only one or two viruses. And it took as long as three months to make.

Wednesday, Leen reported a novel technique to rapidly manufacture so-called virus-specific T cells that can target up to five of the viruses that cause the most trouble for transplant patients: Epstein-Barr virus, adenovirus, cytomegalovirus, BK virus, and human herpesvirus 6.

Essentially, Leen came up with a recipe to stimulate donated T cells in the laboratory so that they better recognize those particular viruses, and then grow large quantities of the cells. It took just 10 days to create and freeze the designer T cells.

To see if they worked, Leen's team treated 11 transplant recipients. Eight had active infections, most with multiple viruses. The cell therapy proved more than 90 percent effective, nearly eliminating all the viruses from the blood of all the patients, Leen reported in the journal Science Translational Medicine.

The other three patients weren't sick but were deemed at high risk. They were given early doses of the T cells protectively and remained infection-free, Leen said.

Next, her team is beginning a bigger step - to try creating a bank of those cells from a variety of healthy donors that any patient could use, without having to custom-brew each dose.

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Stem cell transplantation for severe sclerosis associated with improved long-term survival

By Dr. Matthew Watson

PUBLIC RELEASE DATE:

24-Jun-2014

Contact: Jacob M. van Laar j.m.vanlaar@umcutrecht.nl The JAMA Network Journals

Among patients with a severe, life-threatening type of sclerosis, treatment with hematopoietic stem cell transplantation (HSCT), compared to intravenous infusion of the chemotherapeutic drug cyclophosphamide, was associated with an increased treatment-related risk of death in the first year, but better long-term survival, according to a study in the June 25 issue of JAMA.

Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy (a disorder of the blood vessels), low-grade inflammation, and fibrosis (development of excess fibrous connective tissue) in skin and internal organs. Previously, small studies have shown that systemic sclerosis is responsive to treatment with autologous HSCT, although it has been unclear whether HSCT improves survival, according to background information in the article. For this study, autologous HSCT involved a multistep process beginning with infusion of high doses of cyclophosphamide and an antibody against immune cells, followed by reinfusion of the patient's own stem cells that had been previously collected from blood and purified.

Jacob M. van Laar, M.D., Ph.D., of the University Medical Center Utrecht, Utrecht, the Netherlands and Dominique Farge M.D., Ph.D, of the Assistance Publique - Hopitaux de Paris, Paris 7 Diderot University, France, and colleagues randomly assigned 156 patients with early diffuse cutaneous (widespread skin involvement) systemic sclerosis to receive HSCT (n = 79) or cyclophosphamide (n = 77; 12 monthly infusions). The phase 3 clinical trial was conducted in 10 countries at 29 centers; patients were recruited from March 2001 to October 2009 and followed up until October 2013.

During a median follow-up of 5.8 years, 53 adverse events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). Patients treated with HSCT experienced more adverse events (including death) in the first year but had better long-term event-free survival than those treated with cyclophosphamide.

Patients in the HCST group experienced higher mortality in the first year but had better long-term overall survival than those treated with cyclophosphamide. During year 1 there were 11 deaths (13.9 percent, including 8 treatment-related deaths) in the HSCT group vs 7 (9.1 percent, no treatment-related deaths) in the control group. After year 2 of follow-up, there were 12 deaths (15.2 percent) in the HSCT group vs 13 (16.9 percent) in the control group. After 4 years of follow-up, there were 13 deaths (16.5 percent) in the HSCT group vs 20 (26.0 percent) in the control group.

The authors add that HSCT was also more effective than intravenous cyclophosphamide on measures evaluating skin, functional ability, quality of life, and lung function, consistent with previous studies.

"Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit," the authors conclude.

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Many bodies prompt stem cells to change

By Dr. Matthew Watson

PUBLIC RELEASE DATE:

16-Jun-2014

Contact: David Ruth david@rice.edu 713-348-6327 Rice University

HOUSTON (June 16, 2014) How does a stem cell decide what path to take? In a way, it's up to the wisdom of the crowd.

The DNA in a pluripotent stem cell is bombarded with waves of proteins whose ebb and flow nudge the cell toward becoming blood, bone, skin or organs. A new theory by scientists at Rice University shows the cell's journey is neither a simple step-by-step process nor all random.

Theoretical biologist Peter Wolynes and postdoctoral fellow Bin Zhang set out to create a mathematical tool to analyze large, realistic gene networks. As a bonus, their open-access study to be published this week by the Proceedings of the National Academy of Sciences helped them understand that the process by which stem cells differentiate is a many-body problem.

"Many-body" refers to physical systems that involve interactions between large numbers of particles. Scientists assume these many bodies conspire to have a function in every system, but the "problem" is figuring out just what that function is. In the new work, these bodies consist not only of the thousands of proteins expressed by embryonic stem cells but also DNA binding sites that lead to feedback loops and other "attractors" that prompt the cell to move from one steady state to the next until it reaches a final configuration.

To test their tool, the researchers looked at the roles of eight key proteins and how they rise and fall in number, bind and unbind to DNA and degrade during stem cell differentiation. Though the interactions may not always follow a precise path, their general pattern inevitably leads to the desired result for the same reason a strand of amino acids will inevitably fold into the proper protein: because the landscape dictates that it be so.

Wolynes called the new work a "stylized," simplified model meant to give a general but accurate overview of how cell networks function. It's based on a theory he formed in 2003 with Masaki Sasai of Nagoya University but now takes into account the fact that not one but many genes can be responsible for even a single decision in a cellular process.

"This is what Bin figured out, that one could generalize our 2003 model to be much more realistic about how several different proteins bind to DNA in order to turn it on or off," Wolynes said.

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Promising T cell therapy

By Dr. Matthew Watson

PUBLIC RELEASE DATE:

17-Jun-2014

Contact: Vera Siegler vera.siegler@tum.de 49-892-892-2731 Technische Universitaet Muenchen

This news release is available in German.

The cells of the human immune system are created from special stem cells in the bone marrow. In diseases affecting the bone marrow, such as leukemia, the degenerate cells must be destroyed using radiation or chemotherapy. Subsequently, the hematopoietic system has to be replaced with stem cells from the blood of a healthy donor. Because of the resulting temporary weakening of the immune system, patients are more exposed to viruses that would normally be warded off.

The cytomegalovirus (CMV), which can cause serious damage to lungs or liver in persons with a weakened defense, poses a major clinical problem. In healthy human beings, a CMV infection will usually not produce any symptoms, since the virus is kept at bay by specific immune cells. In their work, the scientists were able to demonstrate that the transfer of just a few specific immune cells is sufficient to protect the recipient with the weakened immune system against infections. To do this, they used T cells that can recognize and kill specific pathogens.

Tested in an animal model

Dr. Christian Stemberger, first author of the study, and his colleagues, first isolated T cells from the blood of healthy donor mice. These immune cells were directed against molecular elements of a bacterial species which normally causes severe infections in animals. The T cells were then transferred to recipient mice that, due to a genetic modification, could no longer produce immune cells of their own similarly to patients suffering from leukemia.

Following the T cell transfer, the researchers infected the treated recipient mice with the bacteria. The results showed that the animals now have effective immune protection against the pathogens, preventing them from becoming ill. "The most astonishing result was that the offspring cells of just one transferred donor cell were enough to completely protect the animals," Christian Stemberger explains.

Successfully used in patients

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Stem cell mobilization therapy may effectively treat osteoarthritis

By Dr. Matthew Watson

PUBLIC RELEASE DATE:

19-Jun-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (June 19, 2014) Researchers in Taiwan have found that peripheral blood stem cells "mobilized" by a special preparation of granulocyte colony-stimulating factor (G-CSF) prior to their injection into rats modeling osteoarthritis (OA), stimulated the bone marrow to produce stem cells, leading to the inhibition of OA progression. The finding, they said, may lead to a more effective therapy for OA, a common joint disease that affects 10 percent of Americans over the age of 60.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1109Deng.

"Currently, OA treatment involves the use of anti-inflammatory drugs, analgesics, lubricating supplements, or surgery," said study lead author Dr. Shih-Chieh Hung of the Department of Medical Research and Education at the Taipei Veterans general Hospital in Taiwan. "Recently, hematopoietic (blood) stem cells derived from bone marrow have emerged as a potential treatment for OA. We hypothesized that G-CSF-mobilized peripheral blood stem cells (gm-PBSCs) contain a population of primitive stem cells that have the capacity for mobility once released from stem cell niches."

While the beneficial effects of G-CSF-mobilized peripheral blood stem cells have been documented when used for treating the negative effects of chemotherapy and radiation, as well as peripheral arterial diseases, this is the first study to investigate the use of gm-PBSCs to treat skeletal diseases, such as OA.

"We demonstrated that PBSCs, mobilized by G-CSF and infused for five days in rats modelling OA, provided a number of beneficial results, including increasing cluster of differentiation 34 positive (CD34+) cell percentages up to 55 fold," reported the authors. "Further, we demonstrated that the progression of OA was inhibited by the gm-PBSCs."

The researchers noted that the use of G-CSF administration in humans to treat other diseases and conditions has been found to be "safe and effective," despite known side effects such as bone pain, headache, fatigue, and nausea which, they added, are generally "transient, self-limiting and without long-term consequences."

"Although potential long-term adverse effects, such as malignancy after G-CSF administration have been reported, the frequency is low and the relationship between major adverse effects and G-CSF administration is not clear," said Dr. Hung.

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2014 Vanderbilt GSC 3MT Finalist: Dikshya Bastakoty – Cardiovascular cell therapy – Video

By Dr. Matthew Watson


2014 Vanderbilt GSC 3MT Finalist: Dikshya Bastakoty - Cardiovascular cell therapy
2014 Vanderbilt GSC 3MT Finalist: Dikshya Bastakoty - Cardiovascular cell therapy: teaching stem cells to fix the broken heart.

By: VanderbiltGSC

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Stem cell-stimulating therapy saves heart attack patients

By Dr. Matthew Watson

PUBLIC RELEASE DATE:

9-Jun-2014

Contact: Kimberly Brown kbrown@snmmi.org 703-652-6773 Society of Nuclear Medicine

St. Louis, Mo. (June 9, 2014) Researchers at the Society of Nuclear Medicine and Molecular Imaging's 2014 Annual Meeting revealed how a protein encourages the production of stem cells that regenerate damaged tissues of the heart following an acute attack (myocardial infarction). They further assert that it has a better chance of working if provided early in treatment. This was confirmed by molecular imaging, which captured patients' improved heart health after therapy.

If given after a heart attack, granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow stem cells that turn down the collateral damage of cell death that occurs after acute myocardial infarction. Other research has shown G-CSF having a beneficial impact on left ventricle ejection fraction, a measurement of how powerfully the heart is pumping oxygenated blood back into the aorta and the rest of the body with each beat. The objective of this study was to find out how beneficial the stem cellstimulating therapy would be if administered early during standard treatment. Early prescription of G-CSF happens to strengthen its effect immediately and after follow up.

"Previous studies have shown that giving G-CSF to unselected heart attack patients failed to satisfactorily improve their condition, but G-CSF may potentially be beneficial if given earlier than 37 hours following myocardial infarction and coronary intervention," remarked Takuji Toyama, MD, the study's principal researcher from the division of cardiology at Gunma Prefectural Cardiovascular Center in Maebashi, Japan. "This study shows that the first intravenous drip infusion of G-CSF during treatment just after hospitalization was able to rescue our patients. I am confident that with additional data from a forthcoming clinical trial, this protocol can be adopted as a standard of practice."

For this study, 40 consecutive patients with acute myocardial infarction were given either G-CSF therapy or saline intravenously for a total of five days beginning during a selected minimally invasive treatment, otherwise known as percutaneous cardiac intervention. Results of one year's worth of SPECT stress tests nailed how earlier start of G-CSF therapy in heart attack patients improves blood flow, access to essential energy and overall cardiac function.

Coronary heart disease caused one out of every six fatalities in the U.S. in 2010, according to 2014 statistics from the American Heart Association. An estimated 620,000 Americans suffered a first heart attack, and 295,000 had a recurrent episode. Collectively, heart attacks occur about once every 34 seconds. Coronary events cause about 379,559 deaths each year.

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Scientific Paper 239: Takuji Toyama, Hiroshi Hoshizaki, Hakuken Kan, Ren Kawaguchi, Hitoshi Adachi, Shigeru Ohsima, Division of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi, Japan; Masahiko Kurabayashi, Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan, "Is the granulocyte colony-stimulating factor therapy in the earliest phase effective to rescue patients with acute myocardial infarction?" SNMMI's 61th Annual Meeting, June 7, 2014, St. Louis, Missouri.

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Researchers developing tiny robotic arm that could fix birth defects in the womb

By Dr. Matthew Watson

LONDON (CNN) Some birth defects in newborns could one day be a thing of the past due to new robotics technologies being developed to perform surgery on babies in the womb.

Spina bifida is one such disease, affecting approximately 1 in 2,500 newborns worldwide, where a lesion on the back leaves the spinal cord exposed in the womb, leading to severe disabilities, learning difficulties, and sometimes death.

The best option is to perform surgery to correct the problem before the baby is born but the complexities of such a procedure mean this currently only takes place in five countries worldwide. Most countries instead perform surgery after a child is born, but when the majority of damage has been done.

To reduce the risk involved in fetal surgery, scientists at University College London (UCL), and KU Leuven in Belgium are developing a miniscule robotic arm to enter the womb with minimum disruption to mother and baby. The robotics are targeting spina bifida but also lesser known conditions such as twin-twin transfusion syndrome, where blood passes unequally between twins who share a placenta, and fetal lower urinary tract obstruction, where babies are unable to urinate in the womb and their bladders become large and distended.

Surgery on fetuses has been effective in treating some conditions to date, but for spina bifida, the risks to mother and baby mean surgery is currently only performed in a handful of countries, where specialist teams exist.

Most birth defects can be prevented if we can intervene earlier, says Professor Sebastien Ourselin, from the UCL Center for Medical Image Computing, who is leading the new research project. But currently, surgical delivery systems are not available and operating on babies in the womb is reserved for just a handful of the most severe defects as risks are too high.

Ourselins team plans to develop a small three-armed robot, no more than 2 cm wide, to allow more surgeries to take place, as part of a $17 million project funded by the Wellcome Trust and Engineering and Physical Sciences Research Council.

The device will consist of a photoacoustic camera that provides 3D imaging of the fetus in real time, which will help guide two flexible arms to deliver gels or patches to seal the gap in the spine of babies with spina bifida. If successful, the arms will be developed with more dexterity and degrees of freedom to perform surgery themselves and treat further conditions such as congenital heart disease. They may even deliver stem cells as stem cell therapies progress. Once entry into the womb becomes safe, the potential is huge.

In countries where fetal surgery is currently performed, surgeons cut into the mothers womb before 26 weeks of pregnancy, but there are health risks, side effects to mothers and risks of pre-term labor.

Where surgery is available in Europe, people are reluctant and fearful of the side-effects, explains Dr. Jan Duprest, who is leading the work at KU Leuvin and has patients declining surgery quite regularly. Robotic surgery is becoming popular these days and we need to take advantage of that and improve not only the number of patients choosing surgery but also improve the freedom with which we can operate using these flexible probes.

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Researchers developing tiny robotic arm that could fix birth defects in the womb

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Shining Light on Madness

By Dr. Matthew Watson

At Novartiss research lab in Cambridge, Massachusetts, a large incubator-like piece of equipment is helping give birth to a new era of psychiatric drug discovery. Inside it, bathed in soft light, lab plates hold living human stem cells; robotic arms systematically squirt nurturing compounds into the plates. Thanks to a series of techniques perfected over the last few years in labs around the world, such stem cellscapable of developing into specialized cell typescan now be created from skin cells. When stem cells derived from people with, say, autism or schizophrenia are grown inside the incubator, Novartis researchers can nudge them to develop into functioning brain cells by precisely varying the chemicals in the cell cultures.

Theyre not exactly creating schizophrenic or autistic neurons, because the cells arent working within the circuitry of the brain, but for drug-discovery purposes its the next best thing. For the first time, researchers have a way to directly examine in molecular detail whats going wrong in the brain cells of patients with these illnesses. And, critically for the pharmaceutical company, there is now a reliable method of screening for drugs that might help. Do the neurons look different from normal ones? Is there a flaw in the way they form connections? Could drugs possibly correct the abnormalities? The answer to each of these questions is a very preliminary yes.

The technique is so promising that Novartis has resumed trying to discover new psychiatric drugs after essentially abandoning the quest. Whats more, its been introduced at a time when knowledge about the genetics behind brain disorders is expanding rapidly and other new tools, including optogenetics and more precise genome editing (see Neurosciences New Toolbox), are enabling neuroscientists to probe the brain directly. All these developments offer renewed hope that science could finally deliver more effective treatments for the millions of people beset by devastating brain disorders.

A revival in psychiatric drug development is badly needed: there hasnt been a breakthrough medicine for any of the common mental illnesses, including schizophrenia, bipolar disorder, or severe depression, in roughly 50 years. From the late 1940s through the 1960s, a series of serendipitous discoveries, beginning with the finding that lithium could help bipolar patients, transformed the treatment of the mentally ill. It became possible to quiet the hallucinations and delusions of schizophrenia and offer a drug to the severely depressed. The sudden availability of pharmacological relief transformed psychiatry and played a role in closing down many of the mammoth mental hospitals of the era. But then, almost as suddenly as it had started, the revolution stalled.

Many of the drugs discovered in the 1950s and 1960s are still the most effective treatments available for schizophrenia, anxiety disorders, and depression. But while these medications have improved the lives of some patients, they are ineffective for others, and they are woefully inadequate in treating many of the worst symptoms. Whats more, the drugs can have severe side effects.

Take schizophrenia, for example. Existing antipsychotic drugs can make the hallucinations and delusions disappear, but they dont improve the so-called negative symptomsthe disruption of emotions such as pleasure, which can leave people uninterested in communicating or even in living. Existing drugs also have no effect on the way schizophrenia can impair concentration, decision-making, and working memory (critical in such tasks as language comprehension). These debilitating cognitive problems make it impossible for people to work and difficult for them even to make the seemingly simple logical choices involved in everyday life. Insidiously, such symptoms can strike high-performing individuals, often in their late teens. People dont understand, says Guoping Feng, a professor of neuroscience at MIT who studies the neural basis of psychiatric disorders. They ask, once a patient is given antipsychotic medicine, Why cant you go to work? But [those with schizophrenia] cant work because they dont have cognitive functions, they dont have normal executive functions. And there are no drugs for this. On top of that are the side effects of antipsychotic medicines, which can include Parkinsons-like movement disorders, dramatic weight gain, or a potentially deadly loss of white blood cells. In short, the illness destroys many patients lives.

We were led down a path that said depression is about being a quart low in serotonin, and schizophrenia means you have a bit too much dopamine on board. But that just isnt how the brain works. The brain isnt a bowl of soup.

Finally, many people with brain disorders are simply not helped at all by available drugs. Antidepressants work well for some people but do nothing for many others, and there are no effective drug treatments for the social disabilities or repetitive behaviors caused by autism.

Overall, neuropsychiatric illness is a leading cause of disability. According to the National Institute of Mental Health (NIMH) in Rockville, Maryland, 26 percent of American adults suffer from a diagnosable mental disorder in any given year. Severe depression, the most common of these disorders, is the leading cause of disability in the U.S. for individuals between 15 and 44. Around 1 percent of the American population suffers from schizophrenia; one in 68 American children is diagnosed with an autism spectrum disorder.

Though the need for better treatments is unquestionable, drug companies had until very recently simply run out of good ideas. The drugs developed in the 1950s and 1960s were discovered by accident, and no one knew how or why they worked. In the subsequent decades, drug researchers reverse-engineered the medications to identify the brain molecules that the drugs acted on, such as dopamine and serotonin. In retrospect, however, scientists now realize that while tweaking the levels of these chemicals addressed some symptoms of psychiatric disorders, it was a crude strategy that ignored the biological mechanisms underlying the illnesses.

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Shining Light on Madness

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Knee and shoulder arthritis/torn rotator cuffs 16 months after stem cell therapy by Dr Harry Adelson – Video

By Dr. Matthew Watson


Knee and shoulder arthritis/torn rotator cuffs 16 months after stem cell therapy by Dr Harry Adelson
Mike discusses his results 16 months after stem cell therapy for his arthritic knees and shoulders and torn rotator cuffs by Dr Harry Adelson at http://www.docerecl...

By: Harry Adelson, N.D.

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Embryonic stem cells offer new treatment for multiple sclerosis

By Dr. Matthew Watson

Scientists in the University of Connecticut's Technology Incubation Program have identified a novel approach to treating multiple sclerosis (MS) using human embryonic stem cells, offering a promising new therapy for more than 2.3 million people suffering from the debilitating disease.

The researchers demonstrated that the embryonic stem cell therapy significantly reduced MS disease severity in animal models, and offered better treatment results than stem cells derived from human adult bone marrow.

The study was led by ImStem Biotechnology Inc. of Farmington, Conn., in conjunction with UConn Health Professor Joel Pachter, Assistant Professor Stephen Crocker, and Advanced Cell Technology (ACT) Inc. of Massachusetts. ImStem was founded in 2012 by UConn doctors Xiaofang Wang and Ren-He Xu, along with Yale University doctor Xinghua Pan and investor Michael Men.

"The cutting-edge work by ImStem, our first spinoff company, demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside," says Professor Marc Lalande, director of the UConn's Stem Cell Institute.

The research was supported by a $1.13 million group grant from the state of Connecticut's Stem Cell Research Program that was awarded to ImStem and Professor Pachter's lab.

"Connecticut's investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research," says Gov. Dannel P. Malloy. "This new study moves us one step closer to a stem cell-based clinical product that could improve people's lives."

The researchers compared eight lines of adult bone marrow stem cells to four lines of human embryonic stem cells. All of the bone marrow-related stem cells expressed high levels of a protein molecule called a cytokine that stimulates autoimmunity and can worsen the disease. All of the human embryonic stem cell-related lines expressed little of the inflammatory cytokine.

Another advantage of human embryonic stem cells is that they can be propagated indefinitely in lab cultures and provide an unlimited source of high quality mesenchymal stem cells -- the kind of stem cell needed for treatment of MS, the researchers say. This ability to reliably grow high quality mesenchymal stem cells from embryonic stem cells represents an advantage over adult bone marrow stem cells, which must be obtained from a limited supply of healthy donors and are of more variable quality.

"Groundbreaking research like this furthering opportunities for technology ventures demonstrates how the University acts as an economic engine for the state and regional economy," says Jeff Seemann, UConn's vice president for research.

The findings also offer potential therapy for other autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and type-1 diabetes, according to Xu, a corresponding author on the study and one of the few scientists in the world to have generated new human embryonic stem cell lines.

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Eye in a Dish: Researchers Make Retina From Stem Cells

By Dr. Matthew Watson

NBC News -- Researchers have grown part of an eye in a lab dish, using a type of stem cell made from a piece of skin.

They said the little retina started growing and developing on its own an important step towards creating custom-tailored organs in the lab.

We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light," said M. Valeria Canto-Soler, an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine.

The team used cells called induced pluripotent stem cells, or iPS cells, which are immature stem cells whose powers resemble those of embryonic stem cells they can morph into any cell type in the body.

Theyre made by tricking an ordinary cell, like a skin cell, into reverting back into embryonic mode. Then the researchers activate genes to get the cell to redirect itself into forming the desired cells in this case cells of the retina.

To the surprise of the researchers, the cells started developing as if they were in a growing human embryo.

"We knew that a 3-D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina, but when we began this work, we didn't think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do, Canto-Soler said in a statement.

The experiment may ultimately lead to technologies that restore vision in people with retinal diseases, she added.

Tests showed the cells responded to light, the team reported in the journal Nature Communications. "Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start," Canto-Soler said.

Other teams have used iPS cells to make a piece of human liver and are using them to study a range of human diseases.

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Eye in a Dish: Researchers Make Retina From Stem Cells

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torn rotator cuff/shoulder arthritis one year after stem cell therapy by Dr Harry Adelson – Video

By Dr. Matthew Watson


torn rotator cuff/shoulder arthritis one year after stem cell therapy by Dr Harry Adelson
Richard discusses his outcome from bone marrow/adipose derived stem cells by Dr Harry Adelson for his torn rotator cuff and arthritic shoulder http://www.docereclinics.com.

By: Harry Adelson, N.D.

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torn rotator cuff/shoulder arthritis one year after stem cell therapy by Dr Harry Adelson - Video

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Leading stem-cell expert to join Stanford Medicine faculty …

By Dr. Matthew Watson

JUNE 5, 2014

BY ERIN DIGITALE

Maria Grazia Roncarolo

Maria Grazia Roncarolo, MD, a stem cell and gene therapy expert and former scientific director of the San Raffaele Scientific Institute in Milan, Italy, is joining the Stanford University School of Medicine as a professor of pediatrics.

Roncarolo has been recruited to lead the schools efforts to translate basic scientific discoveries in the field of regenerative medicine into novel patient therapies, including treatments based on stem cells and gene therapy. My biggest goal is to build an infrastructure and assemble a team of world-class physician-scientists who can take full advantage of the tremendous discovery and knowledge generated at Stanford in order to transfer those into the clinic, she said.

Roncarolo begins June 15 as chief of the newly created Division of Pediatric Translational and Regenerative Medicine within the Department of Pediatrics, and as a pediatric immunologist at Lucile Packard Childrens Hospital Stanford. She will also co-direct Stanfords Institute for Stem Cell Biology and Regenerative Medicine.

Dr. Roncarolo is a world leader in stem cell and gene therapies, said Hugh OBrodovich, MD, professor and chair of pediatrics, and director of the Child Health Research Institute at Stanford. Under her direction, the San Raffaele Scientific Institute has been seminal in showing that these therapies can actually work. Being able to bring her here to Stanford to translate our discoveries into therapies for patients at one of the best childrens hospitals is a perfect match. OBrodovich is also the Adalyn Jay Physician-in-Chief at Lucile Packard Childrens Hospital Stanford.

Stanford is the only institution in the world that has the antibodies required to purify human blood-forming stem cells, giving it a unique advantage in the quest to develop stem-cell-based medical treatments. Roncarolo, meanwhile, has brought many basic-science discoveries in this field to patients. She holds eight patents and has six pending for methods used in cell and gene therapies. She has published more than 280 scientific papers and 22 book chapters. Her publications have been cited more than 19,000 times.

No single person has done as much as she in this field, or as successfully, said Irving Weissman, MD, professor of pathology and of developmental biology, and director of Stanfords Institute for Stem Cell Biology and Regenerative Medicine. Roncarolo will join Michael Longaker, MD, professor of surgery, as a co-director of the institute.

We are very excited that Maria Grazia is joining our faculty, said Lloyd Minor, MD, dean of the School of Medicine. She is an outstanding basic scientist and translational researcher, and a highly knowledgeable institutional leader. She will be a tremendous asset to our team.

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