StemCell Therapy

Public release date: 19-Jun-2012 [ | E-mail | Share ]

Contact: Nicole White nicole.white@cshs.org 310-423-5215 Cedars-Sinai Medical Center

LOS ANGELES (June 19, 2012) Cedars-Sinai's Regenerative Medicine Institute has pioneered research on how motor-neuron cell-death occurs in patients with spinal muscular atrophy, offering an important clue in identifying potential medicines to treat this leading genetic cause of death in infants and toddlers.

The study, published in the June 19 online issue of PLoS ONE, extends the institute's work to employ pluripotent stem cells to find a pharmaceutical treatment for spinal muscular atrophy or SMA, a genetic neuromuscular disease characterized by muscle atrophy and weakness.

"With this new understanding of how motor neurons die in spinal muscular atrophy patients, we are an important step closer to identifying drugs that may reverse or prevent that process," said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute.

Svendsen and his team have investigated this disease for some time now. In 2009, Nature published a study by Svendsen and his colleagues detailing how skin cells taken from a patient with the disorder were used to generate neurons of the same genetic makeup and characteristics of those affected in the disorder; this created a "disease-in-a-dish" that could serve as a model for discovering new drugs.

As the disease is unique to humans, previous methods to employ this approach had been unreliable in predicting how it occurs in humans. In the research published in PLoS ONE, to the team reproduced this model with skin cells from multiple patients, taking them back in time to a pluripotent stem cell state (iPS cells), and then driving them forward to study the diseased patient-specific motor neurons.

Children born with this disorder have a genetic mutation that doesn't allow their motor neurons to manufacture a critical protein necessary for them to survive. The study found these cells die through apoptosis the same form of cell death that occurs when the body eliminates old, unnecessary as well as unhealthy cells. As motor neuron cell death progresses, children with the disease experience increasing paralysis and eventually death. There is no effective treatment now for this disease. An estimated one in 35 to one in 60 people are carriers and about in 100,000 newborns have the condition.

"Now we are taking these motor neurons (from multiple children with the disease and in their pluripotent state) and screening compounds that can rescue these cells and create the protein necessary for them to survive," said Dhruv Sareen, director of Cedars-Sinai's Induced Pluripotent Stem Cell Core Facility and a primary author on the study. "This study is an important stepping stone to guide us toward the right kinds of compounds that we hope will be effective in the model and then be reproduced in clinical trials."

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Cedars-Sinai researchers, with stem cells, advance understanding of spinal muscular atrophy

By Jason Napodano, CFA

Neuralstem, Inc. (NYSE MKT:CUR) has developed a technology that allows large-scale expansion of human neural stem cells ("hNSC") from all areas of the developing human brain and spinal cord. The company owns of has exclusive license to 25 patients and 29 patent applications pending worldwide in the field of regenerative medicine and cell therapy. Management is currently focusing the company's efforts on replacing damaged, malfunctioning, or dead neural cells with fully functional ones that may be useful in treating many central nervous system diseases and neurodegenerative disorders.

Neuralstems lead development program is for Amyotrophic Lateral Sclerosis ("ALS"), also known as Lou Gehrigs disease, named after the famous New York Yankee first baseman who was diagnosed with the disease in 1939, and passed in 1941 at the age of only 37.

ALS Background

ALS is a rapidly progressive neurodegenerative disease characterized by weakness, muscle atrophy and twitching, spasticity, dysarthria (difficulty speaking), dysphagia (difficulty swallowing), and respiratory compromise. The disease is almost always fatal, typically due to respiratory compromise or pneumonia, in two to four years. Initial symptoms of ALS include weakness and/or stiffness followed by muscle atrophy in the arms and legs. This is followed by slurred speech or difficulty swallowing, and loss of tongue mobility. Approximately a third of ALS patients also experience pseudobulbar affect (uncontrollable emotions). As the disease progresses, worsening dysphagia and respiratory failure leads to death. A small percentage of patients may also experience cognitive affects such as frontotemporal dementia and anxiety.

The vast majority (~95%) of cases are idiopathic, although there is a known hereditary factor that leads to familial ALS associated with a defect on the 21st chromosome that accounts for approximately 1.5% of all cases. There are also suspected environmental causative factors, including exposure to a dietary neurotoxin called BMAA and cyanobacteria, and use of pesticides. However, in all cases, the defining factor of ALS is rapid and progressive death of upper and lower motor neurons in the motor cortex of the brain, brain stem, and spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.

Treatment for ALS is limited, and as of today only riluzole, marketed by Sanofi-Aventis as Rilutek, has been found to improve survival to a modest extent (several months). Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. This reduces influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damaged (about 10% incidence).

The remaining treatments for ALS are designed to relieve symptoms and improve quality of life. This supportive care includes a multidisciplinary approach that may include medications to reduce fatigue, control spasticity, reduce excess saliva and phlegm, limit sleep disturbances, reduce depression, and limit constipation. As noted above, median survival is two to four years. In the U.S., approximately 30,000 persons are currently living with ALS.

Neuralstems Approach For ALS

Neuralstem is seeking to treat the symptoms of ALS via transplantation of its hNSCs directly into the gray matter of the patients spinal cord. In ALS, motor neurons die, leading to paralysis. In preclinical animal work, Neuralstem cells both made synaptic contact with the host motor neurons and expressed neurotrophic growth factors, which are protective of cells.

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Neuralstem Pioneering Efforts In ALS

As of now, management is planning to conduct the pivotal program on its own, mostly likely seeking funding through grants with the ALS Association and U.S. National Institutes of Health. However, management is also in discussion with potential pharmaceutical partners on the pivotal program. ALS is a highly attractive area for Big Pharma. Depending on the strength of the phase 1 / 2 data, Neuralstem may be able to strike a commercialization partnership in 2014 to help defer the costs of the planned pivotal trial. We expect that any deal with a larger pharmaceutical company would include a substantial upfront payment that Neuralstem would then use to fund expansion of the development platform into new indications, such as spinal cord injury (IND filed) or stroke.

Market Opportunity

In February 2011, the U.S. FDA granted Neuralstem an Orphan Drug designation for its human spinal cord stem cells (HSSC) for the treatment of ALS. As noted above, there are approximately 30,000 patients in the U.S. living with ALS. We estimate that approximately half of these patients are characterized with an FVC > 60% and may be eligible for treatment with Neuralstems hNSCs. Given the Orphan Drug designation, the limited patient population, and the lack of any meaningful treatment options, we think Neuralstem or its commercialization partner could price this therapy at upwards of $100,000. Therefore, the peak market opportunity for Neuralstem is $1.5 billion.

That being said, drug development in ALS has been a graveyard for pharmaceutical companies. One would assume, based on numerous past clinical failures, that Neuralstems chances in ALS are slim. Small molecules including gabapentin, topiramate, celecoxib, tamoxifen, indinavir, minocycline, and xaliproden, many of which are approved for other indications and have posted annual sales over a billion dollars, have all failed human clinical programs for ALS. Even Vitamin E and Creatine have been tested, to little avail, in ALS. Failed mechanisms of action included calcium channel blockers, glutamate regulators, neuroprotectants, immunosuppressants, GABA receptors, anti-inflammatory agents, and antioxidants.

However, there is one thing in common we see in all of the above failures. They are one molecule targeting one mechanism of action or one pathway. ALS is a high complex and largely uncharacterized disease. Neuralstems approach uses human spinal stem cells that, once injected, can provide multiple mechanisms of action on multiple pathways to affect the disease. Plus, Neuralstems approach is highly targeted, with the cells injected directly into the lumbar or cervical spine. Following grafting, the hypothesis is that the cells rebuild circuitry with the patient motor neurons and protect existing neurons from further degradation. Its clearly a unique approach, and one we believe has a better chance of success than many of the previous failed theories enacted over the past decade.

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CUR - Neuralstem Pioneering Efforts In ALS

Public release date: 19-Jun-2012 [ | E-mail | Share ]

Contact: Jeremy Moore jeremy.moore@aacr.org 215-446-7109 American Association for Cancer Research

LAKE TAHOE, Nev. Results of some preclinical trials have shown that low doses of the antidiabetic drug metformin may effectively destroy cancer stem cells, a group of cells that are considered to be responsible for tumor initiation and, because they are resistant to standard chemotherapies, tumor relapse.

In addition, when metformin was combined with a standard chemotherapy used for pancreatic cancer, the combination treatment was able to efficiently eradicate both cancer stem cells and more differentiated cancer cells, which form the bulk of the tumor, according to data presented by Christopher Heeschen, M.D., Ph.D., at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, held in Lake Tahoe, Nev., from June 18-21, 2012. Heeschen is professor for experimental medicine at the Spanish National Cancer Research Centre in Madrid, Spain.

Most clinical trials of pancreatic cancer conducted during the last 15 years have failed to show marked improvement in median survival, suggesting that the selected approaches were not sufficient for several reasons, according to Heeschen. In recent years, researchers have identified cancer stem cells which, as opposed to the cancer cells that make up the bulk of the tumor, are a small subset of cells that are resistant to conventional therapy.

"Therefore, efficiently targeting these cells will be crucial for achieving higher cure rates in patients with pancreatic cancer," he said. "Our newly emerging data now indicate that metformin, a widely used and well-tolerated drug for the treatment of diabetes, is capable of efficiently eliminating these cells."

Specifically, the researchers found that metformin-pretreated cancer stem cells were particularly sensitive to alterations to their metabolism through the activation of AMPK. In fact, metformin treatment resulted in the death of cancer stem cells. In contrast, treatment of more differentiated cancer cells with metformin only arrested the cells' growth.

"As the cancer stem cells represent the root of pancreatic cancer, their extinction by reprogramming their metabolism with metformin in combination with the stalling of the proliferation of more differentiated cells should result in tumor regression and long-term, progression-free survival," Heeschen said.

The researchers generated data to support this idea when they treated immunocompromised mice implanted with a diverse set of patient-derived tumors with a combination of metformin and gemcitabine, the standard chemotherapeutic treatment for pancreatic cancer. They found that the treatment resulted in reduced tumor burden and the prevention of relapse as compared with treatment with either drug alone.

"Intriguingly, in all tumors treated with metformin to date, relapse of disease was efficiently prevented and there were no noticeable adverse effects," Heeschen said.

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Metformin treatment caused cancer stem cell death in pancreatic cancer cell lines

Featured Article Main Category: Stroke Also Included In: Stem Cell Research;Neurology / Neuroscience Article Date: 17 Jun 2012 - 6:00 PDT

Current ratings for: 'Stroke Treatment Using Stem Cells Shows Early Promise In Controversial Trial'

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The hope is that the treatment, by repairing damaged brain tissue, will one day help stroke patients regain some movement and ability to speak. Even small improvements can make a big difference to a person who has been robbed of the ability to wash, dress and feed themselves.

The PISCES trial (Pilot Investigation of Stem Cells in Stroke) study, which is based in Scotland at the Institute of Neurological Sciences, Southern General Hospital, Greater Glasgow and Clyde NHS Board, is the first in the world to evaluate genetically engineered neural stem cells in people with disabling ischemic stroke.

The researchers presented the interim results at the 10th Annual Meeting of the International Society for Stem Cell Research (ISSR), which took place from 13 to 16 June 2012, in Yokohama, Japan.

The lead investigator of the trial is Professor Keith Muir, SINAPSE Professor of Clinical Imaging, Division of Clinical Neurosciences at the University of Glasgow. He told the press:

"We remain pleased and encouraged by the data emerging from the PISCES study to date."

The Phase I trial, which started towards the end of 2010, and follows five years of repeated regulatory rebuffs, is testing the safety of ReN001, a genetically engineered neural stem cell line made by UK biotech ReNeuron.

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Stroke Treatment Using Stem Cells Shows Early Promise In Controversial Trial

ScienceDaily (June 14, 2012) Six new human embryonic stem cell lines derived at the University of Michigan have just been placed on the U.S. National Institutes of Health's registry, making the cells available for federally-funded research.

U-M now has a total of eight cell lines on the registry, including five that carry genetic mutations for serious diseases such as the severe bleeding disorder hemophilia B, the fatal brain disorder Huntington's disease and the heart condition called hypertrophic cardiomyopathy, which causes sudden death in athletes and others.

Researchers at U-M and around the country can now begin using the stem cell lines to study the origins of these diseases and potential treatments. Two of the cell lines are believed to be the first in the world bearing that particular disease gene.

The three U-M stem cell lines now in the registry that do not carry disease genes are also useful for general studies and as comparisons for stem cells with disease genes. In all, there are 163 stem cell lines in the federal registry, most of them without major disease genes.

Each of the lines was derived from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. The embryos carrying disease genes were created for reproductive purposes, tested and found to be affected with a genetic disorder, deemed not suitable for implantation and would have otherwise been discarded if not donated by the couples who donated them.

Some came from couples having fertility treatment at U-M's Center for Reproductive Medicine, others from as far away as Portland, OR. Some were never frozen, which may mean that the stem cells will have unique characteristics and utilities.

The full list of U-M-derived stem cell lines accepted to the NIH registry includes:

"Our last three years of work have really begun to pay off, paving the way for scientists worldwide to make novel discoveries that will benefit human health in the near future," says Gary Smith, Ph.D., who derived the lines and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute.

"Each cell line accepted to the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines," says Sue O'Shea, Ph.D., professor of Cell and Developmental Biology at the U-M Medical School, and co-director of the Consortium for Stem Cell Therapies.

U-M is one of only three academic institutions to have disease-specific stem cell lines listed in the national registry, says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School. The first line, a genetically normal one, was accepted to the registry in February.

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Six new stem cell lines now publicly available

The graft was accepted by the girl's immune system as it was built from her own cells

By Claire Bates

PUBLISHED: 10:24 EST, 14 June 2012 | UPDATED: 10:35 EST, 14 June 2012

The pioneering technique successfully restored the girl's blood flow

A 10-year-old girl has been given a vein transplant using a blood vessel grown from her own stem cells.

It is the first time such an operation has been undertaken, marking a milestone in tissue engineering.

Similar techniques may in future offer hope for at-risk patients undergoing bypass surgery.

The girl had a blocked hepatic portal vein, which drains blood from the gut and spleen to the liver.

Without treatment, the condition can lead to serious complications including internal bleeding, spleen enlargement and even death.

Traditionally bypass surgery has been used to restore portal blood flow, using sections of vein taken from other parts of the body. This can cause other problems and is not always successful.

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Girl, 10, has vein transplant using a blood vessel grown from her own stem cells

Stem cells are touted as a future source to replenish damaged tissue Researchers find skeletal muscle stem cells can survive for 17 days in human and 16 days in mice This is some two weeks more than the one or two days currently thought 'Highly promising' research requires more testing and validation before it can be tested in humans

By Graham Smith

PUBLISHED: 07:51 EST, 13 June 2012 | UPDATED: 07:52 EST, 13 June 2012

Some stem cells can lay dormant for more than two weeks in a dead person and then be revived to divide into new, functioning cells, scientists revealed yesterday.

The research unlocks further knowledge about the versatility of these cells, touted as a future source to replenish damaged tissue.

The scientists, led by Fabrice Chretien of the Pasteur Institute in Paris, said in a statement: 'Remarkably, skeletal muscle stem cells can survive for 17 days in humans and 16 days in mice post-mortem, well beyond the one to two days currently thought.'

Breakthrough: A fusion of several stem cells - or a myotube - obtained in vitro from a human muscle collected 17 days after an individual's death

The stem cells retained their ability to differentiate into perfectly functioning muscle cells, they found.

The researchers added: 'This discovery could form the basis of a new source, and more importantly new methods of conservation, for stem cells used to treat a number of pathologies.'

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Could dead bodies soon be harvested for their stem cells? Scientists find 'miracle' cells stay alive for 17 days in ...

LONDON: Scientists have successfully transplanted a vein made from a 10-year-old girl's own stem cells into her body. It is the first time such an operation has been reported and marks an important step in the practical ability of doctors to use stem cells to grow replacement cells for damaged or diseased tissue.

Writing in the medical journal The Lancet, a team led by Professor Suchitra Sumitran-Holdgersson, of the University of Gothenburg in Sweden, described how the girl had a blocked hepatic portal vein, which takes blood away from the gut and spleen to the liver.

The blockage can lead to complications including internal bleeding, developmental problems and even death. The usual treatment for the condition is to remove the blocked vein and replace it with sections of healthy vein from other parts of the body.

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The team instead grew a vein for the young girl using her own bone marrow stem cells.

They started with a nine-centimetre section of vein taken from the groin of a donor and stripped it of its cells, leaving behind a tubular protein scaffold. This was seeded with the girl's stem cells and the resulting vein was transplanted into the girl.

The procedure restored blood flow out of her liver immediately.

''The patient increased in height from 137 to 143 centimetres and increased in weight from 30 to 35 kilograms in the one year since the first operation,'' the authors wrote. ''Although we undertook no neurocognitive tests, the parents reported that the patient had enhanced physical activity (increased long distance walks of two to three kilometres and light gymnastics) and improved articulated speech and concentration power in school activities.''

Nine months after the operation, the vein had constricted slightly in size and this was corrected in a follow-up procedure. Most significantly, scientists found no antibodies for the donor vein in the girl's blood. Her body was not rejecting the transplant because it was recognised as being made of her own cells.

''The young girl in this report was spared the trauma of having veins harvested from the deep neck or leg with the associated risk of lower limb disorders, and avoided the need for a liver or multivisceral transplantation,'' Professors Martin Birchall and George Hamilton of University College London wrote in an accompanying commentary article in The Lancet.

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Girl gets vein grown from her own stem cells for transplant

(CBS News) A 10-year-old girl made medical history when a vein created from her own stem cells was transplanted into her body to treat a life-threatening blockage.

PICTURES: First lab-grown windpipe saves cancer patient

The girl had a condition called hepatic portal vein obstruction in which there is a blockage in the vein that drains blood from the intestines and spleen to the liver. A blockage here can lead to major complications like bleeding, developmental delays, an enlarged spleen and even death. Typical treatments include removing veins from other parts of the body - such as the leg - and transplanting them elsewhere to restore blood flow, but the procedures can be risky and have had mixed success.

For the new procedure, the girl was admitted to the Sahlgrenska University Hospital in Gothenburg, Sweden, where a team had already taken a 9 centimeter segment of vein from the groin of a deceased donor. The doctors stripped all cells from the vein, leaving just a tube of scaffolding, which was then injected with stem cells obtained from the girl's own bone marrow. After two weeks in a bioreactor, the graft was re-implanted in the 10-year-old girl, and her condition has been improving ever since.

The medical milestone is described in the June 14 issue of the The Lancet.

"The young girl in this report was spared the trauma of having veins harvested from the deep neck or leg with the associated risk of lower limb disorders," and avoided the need for a liver transplant, explained Dr. Martin Birchall, chair of laryngology, and Dr. George Hamilton, professor of vascular surgery, both at the University College London, U.K., in a commentary published in the same issue.

The girl had no complications from the operation and her blood flow was restored immediately.

In the year since the procedure, the girl has grown from about 4 feet 4.5 inches to almost 4 feet 7 inches and her weight increased from 66 pounds to 77 pounds. However over that year her blood flow decreased and the graft narrowed, requiring a second stem cell-based procedure. She has remained well since the second procedure, taking long walks of up to two miles and participating in light gymnastics. Especially noteworthy is her immune system has not attempted to fight off the donor tissue, despite her not taking any immunosuppressive drugs which often carry side effects.

"The new stem-cells derived graft resulted not only in good blood flow rates and normal laboratory test values but also, in strikingly improved quality of life for the patient," wrote the surgeons, led by Dr. Michael Olausson, a profsesory of surgery at the University of Gothenburg in Sweden. They added that their work opens up the possibility of trying to reproduce arteries for surgical use, such as for coronary bypass surgery.

This isn't the first procedure to use a patient's stem cells to create new tissue to save a person's life. HealthPop reported in 2011 of an Eritrean man with late-stage throat cancer who received the world's first synthetic windpipe. The organ was grown from the man's stem cells and then applied to a plastic scaffold, eliminating the need for a donor organ.

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10-year-old girl gets new vein made from her own stem cells in medical first

Newswise Cell-based therapies have yet to reach their full potential in repairing damaged tissue because of the hostile environment the cells face once injected into the body. A patients inflammatory response normally causes the majority of these therapeutic cells to die or migrate away from the area in need of repair.

To address this problem, a startup company based on technology developed at the Georgia Institute of Technology is creating an efficient, safe and repeatable delivery method that protects cells from death and migration from the treatment site. Using microbead technology developed in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, SpherIngenics is producing protective capsules for the delivery of cell-based therapies.

Supported by a broad range of Georgia Tech initiatives, the company recently received a two-year $730,000 Phase II Small Business Innovation Research (SBIR) grant from the U.S. Department of Defense to continue development of the technology.

When damaged tissue is being repaired by a cell-based therapy, our microbead technology ensures that cells travel to and remain in the targeted area while maintaining continued viability, said SpherIngenics CEO Franklin Bost, who is also a professor in the Coulter Department. This technology has the potential to reduce the cost of treatment by eliminating the need for multiple therapeutic procedures.

Bost and Coulter Department Professors Barbara Boyan and Zvi Schwartz founded the company in 2007. They worked with the Georgia Tech Research Corporation to license five patents from Boyans lab for technology originally developed in the Georgia Tech/Emory Center for the Engineering of Living Tissue (GTEC), which was funded by a grant from the National Science Foundation. Then they secured $450,000, which included a Phase I SBIR grant from the U.S. Department of Defense and grants from the Georgia Research Alliance and the Coulter Foundation.

During Phase I of the SBIR grant, the researchers confirmed that as many as 250 human adult stem cells could remain viable in culture if they were encapsulated in a 200-micron-diameter bead made of natural algae materials and that they could release factors that enhance tissue regeneration.

For the Phase II SBIR grant, were going to examine whether delivering microbeads full of stem cells can enhance cartilage repair and regeneration of craniofacial defects in an animal model, said Boyan, who is the companys chief scientific officer. Boyan is also the associate dean for research and innovation in the Georgia Tech College of Engineering, the Price Gilbert, Jr. Chair in Tissue Engineering at Georgia Tech, and a Georgia Research Alliance Eminent Scholar.

The company will perform this research in its laboratory space located in the Advanced Technology Development Center (ATDC) biosciences incubator.

The companys ultimate goal is to commercialize the microbead technology for use in hospitals and by cell therapy companies. To help reach this goal, a group of students wrote a business plan for SpherIngenics last year through the Georgia Tech College of Managements Technological Innovation: Generating Economic Results (TI:GER) program.

The team -- which included Coulter Department doctoral student Christopher Lee, Georgia Tech MBA students Chris Palazzola and Eric Diersen, and Emory University law students Bryan Stewart and Natalie Dana -- won third place in the 2011 Georgia Tech Business Plan Competition. The competition, while largely an education experience, provided students an opportunity to develop their venture ideas and present them to a panel of highly experienced judges in the venture capital, technology transfer and legal fields.

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Georgia Tech Cell Delivery Startup Secures Defense Funding

Public release date: 11-Jun-2012 [ | E-mail | Share ]

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. When most groups of mammalian cells are faced with a shortage of nutrients or oxygen, the phrase "every man for himself" is more apt than "all for one, one for all." Unlike colonies of bacteria, which often cooperate to thrive as a group, mammalian cells have never been observed to help one another out. But a new study led by a researcher at the Stanford University School of Medicine has shown that certain human embryonic stem cells, in times of stress, produce molecules that not only benefit themselves, but also help nearby cells survive.

"Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants," said Stanford postdoctoral scholar Bikul Das, MBBS, PhD. "But in mammalian cells at the cellular level the idea of altruism has never been described before." Das is the lead author of a paper, to be published online June 11 in Stem Cells, documenting altruistic behavior by human embryonic stem cells, or hESCs.

While altruism is generally thought of as a virtue, it can have a downside for hESCs: The altruistic cells appear to be more prone to accumulating mutations, a sign that they could lead to cancers. A better understanding of hESC altruism could provide new insights into cancer therapies, as well as improving scientists' ability to develop safe and effective stem cell treatments for other diseases.

The finding arose from Das' research into how hESCs react to low-oxygen environments, important because many cancerous tumors are low in oxygen. Embryonic stem cells have the capability to develop into many different cell types through a process called differentiation. Das found that when hESCs were placed for 24 hours in an environment with only one-tenth of a percent of oxygen (the air we breathe, by comparison, is almost 21 percent oxygen), free-radical molecules were generated that began causing internal damage in some cells. Ninety percent of the hESCs differentiated into other cell types or died, with only 10 percent maintaining their so-called "stemness," meaning they retained their ability to develop into any type of cell.

Das wanted to know what set these more hearty cells apart and so began sorting them based on what molecules they contained.

Das and his colleagues discovered that of the embryonic stem cells that had survived the oxygen deprivation, half had high levels of HIF2-alpha (a protein that turns up the production of antioxidant molecules) and low levels of p53 (a protein that normally encourages cells to die when they have too much DNA damage). These levels of HIF2-alpha and p53 are enough, Das showed, to keep the cells from differentiating by turning off cellular pathways typically involved in the process.

But the other half of the stem cells that had kept their "stemness" had relatively normal levels of HIF2-alpha and p53, he and his colleagues report in their paper. There was no clear explanation as to how they would remain undifferentiated without the help of high HIF2-alpha and low p53 unless the other cells were helping them out.

"When I saw this data, I began to suspect that maybe there was altruism going on," said Das.

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Stanford researcher identifies unusual 'altruistic' stem cell behavior with possible link to cancer

ScienceDaily (June 11, 2012) When most groups of mammalian cells are faced with a shortage of nutrients or oxygen, the phrase "every man for himself" is more apt than "all for one, one for all." Unlike colonies of bacteria, which often cooperate to thrive as a group, mammalian cells have never been observed to help one another out. But a new study led by a researcher at the Stanford University School of Medicine has shown that certain human embryonic stem cells, in times of stress, produce molecules that not only benefit themselves, but also help nearby cells survive.

"Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants," said Stanford postdoctoral scholar Bikul Das, MBBS, PhD. "But in mammalian cells -- at the cellular level -- the idea of altruism has never been described before." Das is the lead author of a paper, published online June 11 in Stem Cells, documenting altruistic behavior by human embryonic stem cells, or hESCs.

While altruism is generally thought of as a virtue, it can have a downside for hESCs: The altruistic cells appear to be more prone to accumulating mutations, a sign that they could lead to cancers. A better understanding of hESC altruism could provide new insights into cancer therapies, as well as improving scientists' ability to develop safe and effective stem cell treatments for other diseases.

The finding arose from Das' research into how hESCs react to low-oxygen environments, important because many cancerous tumors are low in oxygen. Embryonic stem cells have the capability to develop into many different cell types through a process called differentiation. Das found that when hESCs were placed for 24 hours in an environment with only one-tenth of a percent of oxygen (the air we breathe, by comparison, is almost 21 percent oxygen), free-radical molecules were generated that began causing internal damage in some cells. Ninety percent of the hESCs differentiated into other cell types or died, with only 10 percent maintaining their so-called "stemness," meaning they retained their ability to develop into any type of cell.

Das wanted to know what set these more hearty cells apart and so began sorting them based on what molecules they contained.

Das and his colleagues discovered that of the embryonic stem cells that had survived the oxygen deprivation, half had high levels of HIF2-alpha (a protein that turns up the production of antioxidant molecules) and low levels of p53 (a protein that normally encourages cells to die when they have too much DNA damage). These levels of HIF2-alpha and p53 are enough, Das showed, to keep the cells from differentiating by turning off cellular pathways typically involved in the process.

But the other half of the stem cells that had kept their "stemness" had relatively normal levels of HIF2-alpha and p53, he and his colleagues report in their paper. There was no clear explanation as to how they would remain undifferentiated without the help of high HIF2-alpha and low p53 -- unless the other cells were helping them out.

"When I saw this data, I began to suspect that maybe there was altruism going on," said Das.

To test the theory, Das and his colleagues at the University of Toronto, where he began the work as a graduate student, let the cells with high levels of HIF2-alpha and low levels of p53 soak in a cell culture medium for 24 hours. Then, he removed the cells and added the other half -- those that didn't have high HIF2-alpha and low p53. Sure enough, when the mixture was deprived of oxygen, the cells retained their stemness. Molecules in the liquid had some property that kept them from differentiating. The team discovered that the important molecule in the liquid is an antioxidant called glutathione.

Scientists had previously shown that when embryonic stem cells are under stress, levels of HIF2-alpha and p53 increase and most cells differentiate or die. What makes this study unusual is that Das and colleagues were able to isolate the altruistic cells that exhibit low levels of p53, which helps them to escape death or differentiation.

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Unusual 'altruistic' stem cell behavior with possible link to cancer identified

BONITA SPRINGS -

An attorney for the Bonita Springs doctor accused of performing controversial stem cell treatment on a patient who then died expects depositions to be taken this week that he says will help clear his client's name.

Dr. Zannos Grekos had his medical license suspended back in March after a patient, 77-year-old Richard Poling, died following an injection of his own stem cells.

Documents posted on the Department of Health's website show that Poling paid $8,000 by wire transfer to have his own stem cells removed from his body and sent by courier to a lab in Boynton Beach. The cells were to be processed and returned the same day.

According to the documents, Poling had stomach pains before his cells were returned. Doctors discovered the man had a hematoma, and made him comfortable while he waited for his tissue to be returned for re-injection.

The Department of Health found the laboratory used to process the cells "turned out to be a small office in a strip mall" and "the person that allegedly operated the machine that performed the ultrasonic cavitation on the sample of R.P.'s tissue was unsupervised and was not licensed either by the Florida Board of Medicine or by the Florida Board of Clinical Laboratory Personnel."

Further, documents state the stem cell material was not tested, only visually inspected before being brought back to Bonita Springs.

Poling went into cardiac arrest as the cells were injected into his body.

The Department of Health report states the stem cells were found during autopsy in the pulmonary arteries and capillaries.

Grekos' attorney says the clinician who worked at the Boynton Beach lab did not need a license. He tells NBC2 the clinician and an assistant will be interviewed this week by the Department of Health. Department officials have not confirmed that information.

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New details in Grekos patient death case

Editor's Choice Main Category: Cardiovascular / Cardiology Article Date: 08 Jun 2012 - 12:00 PDT

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The research is profound because it contradicts much of the generally accepted theories of what causes arterial hardening, and the concept may also relate to many other diseases could the associated stem cells be pinpointed.

What senior author Song Li, a bioengineering professor at UC Berkeley and a researcher at the Berkeley Stem Cell Center, and his team have uncovered is a dormant stem cell in blood vessel walls, that seems to sit inactive for most of a person's lifetime, before coming to life and causing less functional cells to begin to grow. Li says these new types of cells that start growing in later life, are the root cause of arterial hardening and clogging that are associated with deadly strokes and heart attacks.

Originally, it was thought that the smooth muscle cells in the arteries lining become scarred over time, and this leads to the narrow and brittle arteries that play a major part in causing cardiovascular disease. Not so says Liu: Essentially, what the scientists are saying is that the smooth muscle cells are not to blame. Rather a different kind of stem cell, that Li calls multipotent vascular stem cells, kicks in, and begins growing cells that look much like the smooth muscle cells, but don't function correctly. The cells were not found previously, because there are so few of them, that they were hard to isolate.

Li continues:

It almost sounds like something from Bladerunner, where the replicant humans have been deliberately designed to deteriorate and die at a much faster rate than the natural ones. What purpose would it serve the body under standard evolutionary terms to have cells activating later in life that effectively lead to its demise? With the arteries poorly formed, with wrong cell types, the blood flow becomes slowed and can then stopped completely. This causes strokes or heart attacks, depending on the location of the blockage. Strokes and heart attacks are one of the leading causes of death in the United States.

Creating drugs or other genetic treatments to shut down these stem cells or even deactivate them while a person is still young has the potential in the future to prevent arteriole hardening, reverse the damage already done, and even make this type of cardiovascular disease a thing of the past. Perhaps the futuristic Woody Allen movie "Sleeper" where people smoke tobacco and eat a high fat diet because it's healthier is not so far fetched after all.

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Scientists Say They Found A Stem Cell That Causes Heart Disease

UC Berkeley scientists have discovered a type of stem cell that appears to lie dormant in blood vessel walls for decades before waking up and causing the arterial hardening and clogging that are associated with deadly strokes and heart attacks.

The findings, published Wednesday in the journal Nature Communications, go against the prevailing theory on the cause of heart disease - that the smooth muscle cells that line blood vessels become damaged over time and are triggered to proliferate. Those smooth muscle cells were thought to build up like scar tissue and cause the blood vessels to become narrow or brittle.

The new theory suggests that the smooth muscle cells found in the blood vessel walls aren't to blame, but rather a small cluster of stem cells is. It's those stem cells that proliferate and cause damage, and they should be the target of drug therapies to treat, and potentially cure, heart disease, the UC Berkeley scientists say.

"We call them sleeping beauty or sleeping evil cells, because they don't do anything when they're dormant. The stem cells stay quiescent for decades before they start to grow and they make the blood vessels harden," said senior author Song Li, a bioengineering professor at UC Berkeley and a researcher at the Berkeley Stem Cell Center.

"These stem cells are probably less than 5 percent of the cells in the blood vessel when they're dormant," Li said. "But they can dominate. They can become the major cell."

Li and his team still believe that smooth muscle cells are to blame for much of the damage in the blood vessels. What's changed is where those cells come from.

Scientists have known for decades that the blood vessel damage associated with heart disease is caused by a buildup of smooth muscle cells. Those clumps of cells cause the blood vessel to become dangerously narrow, hindering the flow of blood, or they become brittle clots that break off and block vessels entirely.

When the blood flow is slowed or stopped completely, it can cause strokes or heart attacks, depending on the location of the blockage. Strokes and heart attacks are among the most common causes of death in the United States.

The stem cells, which Li and his team have named multipotent vascular stem cells, remained undiscovered because so few of them exist when they're dormant. It didn't help that after they become activated, they look very similar to the smooth muscle cells that scientists have long thought were the culprit in heart disease.

The prevailing theory has been that damage to the blood vessel caused the smooth muscle cells in the vessel walls to "de-differentiate," or revert to an earlier stage of development that allows them to reproduce and build the scar-like tissue. But there was no proof of it, Li and others noted.

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Type of stem cell may contribute to heart disease

By LINDSAY PETERSON | The Tampa Tribune Published: June 06, 2012 Updated: June 06, 2012 - 8:00 AM

The computer screen on the desk at the University of South Florida shows a smattering of multicolored dots.

A mass of green ones clusters at the bottom of the image, which shows the brain of a research rat. But here and there, several of the dots seem to be moving up, migrating to an area of the brain that has been damaged.

These green dots represent stem cells, the kind that exist naturally deep inside the brain and have the ability to transform themselves into healthy brain cells.

Their migration on the image means that doctors may one day be able to treat traumatic brain injury with a simple substance: oxygen.

USF researcher Cesar Borlongan and his colleagues are experimenting with the use of hyperbaric chambers. They're working with rats now, treating them after a brain injury, then examining them for signs of change. But they expect to connect the dots all the way to apply their findings to veterans, stroke victims and others who've suffered brain trauma.

Patients in hyperbaric chambers breathe in oxygen at high pressure, which pushes it into their bloodstream and tissues.

Hyperbaric treatments are used today for crash wounds, burns, even anemia, said Raffaele Pilla, one of the USF researchers on the project.

Research shows it also can help traumatic brain injury sufferers. The federal government still considers it experimental, but the studies "are compelling enough to mandate expedited research trials," said a U.S. Veterans Administration report in 2010.

The USF study is part of a major effort to find treatments for battlefield injuries, Borlongan said. It's created a Veterans Reintegration and Resilience program that pulls together researchers from many disciplines, from brain research to drug development to physical rehabilitation.

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Researchers working to repair brain injuries

Scientists previously thought heart attacks and strokes were caused by smooth muscle cells Stem cells multiply and caused arteries to harden Heart attacks affect 90,000 and strokes 150,000 in Britain every year

By Emma Reynolds

PUBLISHED: 11:17 EST, 6 June 2012 | UPDATED: 11:17 EST, 6 June 2012

The real culprit behind heart attacks and strokes is stem cells, researchers have claimed in a landmark study that could revolutionise treatment.

Until now, scientists thought vascular health problems were triggered by smooth muscle cells.

Now a team from the University of California in Berkeley have found a previously unknown stem cell, which causes the arteries to harden when it multiplies.

Real hope: The cells can multiply and cause arteries to harden, blocking the blood's route to the heart or brain

The groundbreaking work is set to completely change how heart attacks and strokes are treated, dramatically cutting the number of deaths, according the study published today in the journal Nature Communications.

Heart attacks are the most common reason for people to need emergency treatment. Around 90,000 people in Britain have one each year - of whom around a third will die as a result.

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Stem cells are identified as real culprit behind heart attacks after case of mistaken identity that could ...

PITTSBURGH (KDKA) Injecting stem cells into the brain of someone who has had a stroke is a hot button issue.

Is it safe? Can it be done?

Thats what researchers at the University of Pittsburgh are trying to find out.

Because these are cells that have not been injected into the brain before, we need to know whether it is safe to do so, UPMC neurologist Dr. Lawrence Wechsler said.

So far, at UPMC, two people have received injections of stem cells from the bone marrow of healthy adult donors.

Roger Hill is one of them.

In August 2009, he woke up with a stroke. The first thing he noticed was his vision. He couldnt see half of his world and then his left side left him.

Something happened with my left leg. I fell down, he said. I couldnt feel my left knee.

The problem was in the brain.

A stroke most commonly happens because of a blocked artery. Part of the brain dies from a lack of oxygen and blood flow. Stroke is a leading cause of death and disability.

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Researchers Testing Stem Cells As Treatment For Stroke Recovery

Public release date: 4-Jun-2012 [ | E-mail | Share ]

Contact: David Eve Celltransplantation@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (June 4, 2012) When autologous (self-donated) lung-derived mensenchymal stem cells (LMSCs) were transplanted endoscopically into 13 adult female sheep modeled with emphysema, post-transplant evaluation showed evidence of tissue regeneration with increased blood perfusion and extra cellular matrix content. Researchers concluded that their approach could represent a practical alternative to conventional stem cell-based therapy for treating emphysema.

The study is published in Cell Transplantation (21:1), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"Mensenchymal stem cells are considered for transplantation because they are readily available, highly proliferative and display multi-lineage potential," said study corresponding author Dr. Edward P. Ingenito of the Brigham and Women's Hospital Division of Pulmonary and Critical Care Medicine. "Although MSCs have been isolated from various adult tissues - including fat, liver and lung tissues - cells derived from bone marrow (BM) have therapeutic utility and may be useful in treating advanced lung diseases, such as emphysema."

However, according to the authors, previous transplantation studies, many of which used an intravenous delivery method, have shown that BM-MSCs have been only marginally successful in treating lung diseases. Further, therapeutic responses in those studies have been limited to animal models of inflammatory lung diseases, such as asthma and acute lung injury.

To try and answer the questions surrounding the utility of BM-MSCs for treating advanced emphysema, a disease characterized by tissue destruction and loss of lung structural integrity, for this study the researchers isolated highly proliferative, mensenchymal cells from adult lung parenchyma (functional tissue) (LMSCs) and used an endoscopic delivery system coupled with a scaffold comprised of natural extracellular matrix components.

"LMSCs display efficient retention in the lung when delivered endobronchially and have regenerative capacity through expression of basement membrane proteins and growth factors," explained Dr. Ingenito.

However, despite the use of autologous cells, only a fraction of the LMSCs delivered to the lungs alveolar compartment appeared to engraft. Cell death likely occurred because of the failure of LMSCs to home to and bind within their niche, perhaps because the niche was modified by inflammation or fibrosis. These cells are attachment-dependent and failure to attach results in cell death."

Their findings did suggest, however, that LMSCs were capable of contributing to lung remodeling leading to documented functional improvement rather than scarring 28 days post transplantation.

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Cell transplantation of lung stem cells has beneficial impact for emphysema