January 24, 2012 by

Medistem and Licensee ERCell Receive Russian Regulatory Approval for the RECOVER-ERC Trial

The clinical trial, Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC), is being led by Principle Investigator Dr. Leo Bockeria, Chairman of the Backulev Center http://www.bakulev.ru/en/about/director/.

The Backulev Center is Russia’s premier institute for cardiovascular surgery and cardiology. Every year the Backulev Center performs approximately 30,000 diagnostic and treatment procedures, which includes 7,000 open heart surgeries and more than 12,000 angioplasties.

The RECOVER-ERC trial will recruit 60 patients with congestive heart failure, and randomize the patients into 3 groups of 20 patients each. Group 1 will receive 50 million ERC, Group 2 will receive 100 million and Group 3 will receive 200 million. Each group will have 15 patients receiving cells and 5 patients receiving placebo. Efficacy endpoints include ECHO and MRI analysis, which will be conducted at 6 months after treatment.

“I joined Medistem and personally invested into the company because of its strong science and intellectual property position. It is this strong science that has allowed for such a rapid progression of the ERC product from discovery, to animal studies, and now to approval for initiation of efficacy finding studies,” said Dr. Vladimir Bogin, President and Chairman of Medistem, and a Yale-trained physician practicing in the USA. “As a medical doctor I see the suffering and lack of options for patients with CHF. I am proud that our team is able to offer hope.”

This is the second clinical trial that Medistem has been granted approvals for. In September 2011, the company received FDA clearance for beginning a 15 patient trial treating critical limb ischemia patients together with Dr. Michael Murphy at Indiana University.

“We are especially grateful to our Russian licensee ERCell LLC which has worked intensely with our CRO and the Backulev Center in laying down the groundwork for this approval,” said Vladimir Zaharchook, Vice President and Vice Chairman of Medistem. “To our knowledge, ERCell is the only company in Russia working on a stem cell product that can be reproducibly manufactured, frozen, and sold as a drug, not a procedure.”

“This approval is a key milestone for ERCell. Given that Russia has one of the highest incidences of heart failure per capita in the world, we are confident that we can make a difference in patients’ lives and position Russia as an international leader in cell therapy,” said Tereza Ustimova, CEO of ERCell.

About Medistem Inc.
Medistem Inc. is a biotechnology company developing technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company’s lead product, the endometrial regenerative cell (ERC), is a “universal donor” stem cell being developed for critical limb ischemia. A publication describing the support for use of ERC for this condition may be found at http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf. ERC can be purchased for scientific use through Medistem’s collaborator, General Biotechnology http://www.gnrlbiotech.com/?page=catalog_endometrial_regenerative_cells.

Cautionary Statement
This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

Filed Under: Adult Stem Cells, Heart Disease, News, Stem Cell Research Tagged With: , , , , , ,
January 16, 2012 by

Blood from young mice helps older mice with multiple sclerosis

A new mouse study has shown that blood from young mice helps old mice to heal damage caused by MS.

MS causes myelin, which insulates nerve cells electrically, to become damaged. Stem cells can produce myelin but they lose efficiency in older patients.

Researchers in the UK have found a way to reverse this age-related efficiency loss. By linking the bloodstreams of young mice to old mice with myelin damage, the older stem cells were reactivated and boosted myelin production.

White blood cells from the young mice called macrophages were found at myelin damage sites in the old mice. These cells engulf and destroy pathogens and debris, including destroyed myelin.

Amy Wagers, from Harvard University says, “We know this debris inhibits regeneration, so clearing it up is important.”

Filed Under: Multiple Sclerosis, News, Stem Cell Research Tagged With: , , , , ,
December 8, 2011 by

Adult Stem Cell Clinical Trials Showing Success

A Number of Clinical Trials Using Adult Stem Cells Are Showing Early Success

Dozens of adult stem cell treatments are moving through clinical trials and showing early success, raising hopes that some could reach the market within five years. ‘It will only take a few successes to really change the field,’ said Gil Van Bokkelen, chief executive of Athersys and chairman of the Alliance for Regenerative Medicine. ‘As you see things getting closer and closer to that tipping point, you’re going to see a frenzy of activity take place.’ Many of the trials focus on heart disease and inflammatory conditions, some of the biggest markets in medicine. The cells used are derived from adult tissue such as fat, or bone marrow, thereby circumventing the ethical concerns raised by the use of cells derived from embryos.

Data for the most part remains early, but as more results emerge, pharmaceutical companies are beginning to take note. ‘A lot of big companies are looking to place bets on some Phase II products once that data has been confirmed,’ said Paul Schmitt, managing partner at Novitas Capital. ‘Even now they’re attending all the medical meetings and talking to all the stem cell companies.’ Steven Martin, from Aspire Capital Partners LLC said they were willing to be patients as the benefits from treatment could be enormous. ‘My philosophy in the stem cell space is that it’s very difficult at this point to pick the winners and losers,’ he said. ‘We believe that over time there will be some very significant clinical progress, and valuations will improve, but we’re still a long way from an approved therapy.’

Aastrom Biosciences recently presented promising results from a mid-stage trial of its treatment for patients with critical limb ischemia, a disease in which blood flow to the extremities is restricted, at the American Heart Association’s annual meeting. A mid-stage trial from Australia’s Mesoblast Ltd showed its stem cell product reduced the rate of heart attacks and the need for artery clearing procedures by 78 per cent. ‘We’re actually developing products now,’ said Timothy Mayleben, chief executive of Aastrom, which is using cells derived from a patient’s own bone marrow to develop treatments for cardiovascular disease. ‘For the first time you are starting to see data being presented at major medical meetings.’ Pfizer Inc, Johnson & Johnson and Roche Holding AG are members of the Alliance for Regenerative Medicine, a nonprofit group that promotes awareness of the field. Pfizer has a regenerative medicine unit and a partnership with Athersys. But their projects are small as they want to wait to see data in hundreds of patients. The promise of stem cells, which have been used for 40 years in bone marrow transplants, lies in their ability to repair tissue, reduce inflammation, regulate the immune system, and respond to calls for help from multiple places inside the body. Stem cells are the body’s master cells – blank slates that renew themselves and mature into specific cell types in the heart, muscle and other organs.

Embryonic stem cells are uniquely capable of differentiating into every type of mature cell in the body, and were long viewed as the most promising for regenerating tissue. But harvesting stem cells from embryos requires the destruction of the embryo itself, a process opposed by conservative Christian groups. Moreover, their endless capacity to divide can lead to the formation of teratomas, or stem cell cancers. Recently, Geron Corp, the world’s leading embryonic stem cell company, said it could no longer fund its stem cell work and would focus on developing cancer drugs. It closed its trial for spinal cord injury. Unlike embryonic stem cells, adult stem cells have a more limited capacity to differentiate, but appear able to reduce inflammation and promote blood vessel formation. Furthermore, they can respond to damage in the body in a flexible and dynamic way, offering advantages over traditional drugs.
‘They seem to be preprogrammed to act some way in tissue repair, not to form an organ or a tissue,’ said Douglas Losordo, head of stem cell research at Baxter International Inc, which is developing cell therapies for heart disease. ‘The cells that we use are very effective at stimulating the formation of new blood vessels, but if I wanted to make a brain cell out of those cells they would not be very good at it.’ These are the type of stem cell treatments, delivered by infusion, injection or catheter, that are being developed today.
‘We wanted to create a product that everyone could receive and not have to match every donor to every recipient,’ said Robert Hariri, chief executive of Celgene’s Cellular Therapeutics unit.

Different types of stem cell are being used for different diseases. Cytori Therapeutics is developing a heart disease product derived from fat cells, for example, while Celgene is using placental cells for Crohn’s disease and rheumatoid arthritis therapies. Fetal cells are also being explored. Neuralstem Inc, for example, is developing treatments for neurological disorders from an aborted fetus. As cell therapies move further through clinical trials, companies will need more money, and funding is scarce.
Yet even if companies remain afloat long enough to bring a product through late-stage clinical trials, it is unclear what regulators like the Food and Drug Administration will require in order to approve them Some believe the regulatory hurdles for treatments derived from a patient’s own cells will be lower than those where the cells come from donors, since there is less risk of cell rejection. However, no clear pathway has yet been established. ‘We need a clear, consistent and rigorous regulatory framework,’ said Athersys’s Van Bokkelen. ‘The FDA is actually willing to provide lots of guidance and assistance to sponsors, if you just ask them.’

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , , , ,
December 6, 2011 by

Healing juices’ of stem cells could help treat asthma

Research suggests future use of cells in kidney, heart disease
BY BRENT WITTMEIER, EDMONTON JOURNAL DECEMBER 2, 2011

University of Alberta pediatric asthma researcher says that the medical benefits of stem cells may lie in their by-product “healing juices”.

Dr. Bernard Thébaud believes the by-products of mesenchymal stem cells – found in umbilical cord tissue and with known anti-inflammatory characteristics – could possibly heal lungs inflamed by chronic and acute asthma.

The findings, published in the American Journal of Respiratory Cell and Molecular Biology, look at the effects of what Thébaud called “healing juices” on refractory asthma, a form of the disease that is particularly difficult to treat with inhalers.

Thébaud, a neonatal pediatrician and professor of pediatrics at the University of Alberta Faculty of Medicine and Dentistry, said the cells and their juices are easily isolated and cultivated in the lab.

“We cultured the cells in the petri dish, and instead of taking the cells, we just took what the cells produced, the juice they were basically swimming in,” Thébaud said. “We compared that to control cells cultured the same way, but didn’t have that same effect.”

Thébaud’s team created asthma in lab mice, then injected the juices through their noses. The by-products opened airways, restored breathing and reduced inflammation in their lungs.

Thébaud began researching pediatric lung disease in 2002, adding the “exciting” discipline of stem-cell research two years later. The new study builds on some of Thébaud’s previous research into how stem cells work.

“Initially we thought you have to give the cells (to the patient) because they replace dead cells,” he said. “That’s not actually the case.”

Thébaud initially used the mesenchymal stem cells in a study of newborn lung injury, discovering “tremendous benefits” for the health of the lungs. But when his research team tried to see where those stem cells were, they couldn’t find them.

“Maybe they don’t replace dead cells. Maybe they sit there and produce juices, then vanish,” he said.

Although the research is still at an early stage, Thébaud said his hope is for a “super-inhaler” five to 10 years from now that would heal inflammation, boost healthy cells and aid in breathing. He hopes to live the researcher’s dream and drive the discovery from his lab into the clinic.

His goal “would be to have a puffer with stem cell by-products that would prevent those symptoms of asthma,” he said.

Thébaud is convinced it could work. But exactly which compounds or factors are doing the “healing” is hardly academic, and will likely form the next stage in the research.

“It is the question,” said Thébaud. “First, we have to know should we not give the cells, or can we just deliver the juices. Do we have to know what’s in there?”

That question could also delay clinical research by an additional five years, the time he estimates it would take to synthesize the factor pharmaceutically. He will be discussing the study with Health Canada to determine barriers to clinical research using just undifferentiated by-products.

Thébaud also believes the approach demonstrates “many therapeutic avenues” beyond asthma, which affects an estimated 300 million people worldwide. The potential of stem-cell research isn’t yet known.

“It’s up to us now to harness the healing powers of these cells,” he said.

“We know it works in a variety of lung diseases. By extension, we know it will work in kidney, or heart or brain disease as well.”

Filed Under: Adult Stem Cells, Asthma, News, Stem Cell Research Tagged With: , , , , ,
May 31, 2011 by

Blood Vessels Made from Embryonic Stem Cells are Different than Naturally Occurring Blood Vessels

Glaser et al. J Vasc Res. 2011 May 31;48(5):415-428.
In addition to ethical dilemmas associated with embryonic stem cells, there are ample data demonstrating at administration of these cells causes formation of aggressive tumors called teratomas. One way in which scientists are trying to “tame” these cells is to reprogram them in the test tube. Conceptually if you can develop a stable population of cells in vitro, then these can be expanded and used clinically. Still the issue comes up whether the embryonic stem cell derived cells have a higher predisposition to cancer. This indeed may be the case because it takes many years for an embryonic stem cell to become an adult cell naturally, whereas in vitro generated cells are “hyperaccelerated” to maturity. The possibility that in vitro generated cell products from embryonic stem cells have abnormalities is supported by research showing that cells derived from embryonic stem cells actually have a lower potential to stimulate the immune system as compared to equivalent tissue. In other words, cardiac cells generated from embryonic stem cells are less visible to the immune system compared to cardiac cells from an adult.
In a recent study Glaser et al. Functional Characterization of Embryonic Stem Cell-Derived Endothelial Cells. J Vasc Res. 2011 May 31;48(5):415-428, scientists from the University of California Merced have used embryonic stem cells to generate blood vessel cells called endothelial cells. Endothelial cells are very important from a therapeutic point of view because they can be used to treat diseases of poor circulation. These include angina, limb ischemia and some types of heart failure.
The scientists compared the biological activities of endothelial cells generated from embryonic stem cells with those of naturally occurring cultured mouse aortic endothelial cells. They showed that the embryonic stem cell generated endothelial cells produce less NO on a per cell basis, increased angiogenic sprouting and are more resistant to inflammatory signals. They also found that the embryonic stem cell derived endothelial cells possessed a higher propensity towards the venous endothelial lineage as compared to aortic endothelium. These studies suggest that it is still difficult to replicate generation of adult cells from embryonic stem cells.

Filed Under: News, Stem Cell Research Tagged With: , , , ,
May 31, 2011 by

How Bone Marrow Stem Cells Help in Stroke Recovery

Nakano-Doi et al. Stem Cells 28(7):1292-302. May 2011
Scientists from the Institute for Advanced Medical Sciences of Hyogo, Japan have announced new research findings suggesting that bone marrow stem cells may be useful in the treatment of stroke. Although other scientists have previously demonstrated similar findings, including in patients, (Suárez-Monteagudo et al. Restor Neurol Neurosci. 2009;27(3):151-61), what is astonishing about the current work is that an actual biological mechanism by which the stem cells are functioning is proposed.
In the paper Nakano-Doi et al. Bone marrow mononuclear cells promote proliferation of endogenous neural stem cells through vascular niches after cerebral infarction. Stem Cells 28(7):1292-302. May 2011, the scientists induced stroke in mice by tying up the middle cerebral artery. This causes damage to approximately the same area that gets damaged in humans who have a stroke. Two days after inducing this “artificial stroke”, the scientists injected the mice with 1 million bone marrow mononuclear cells (BMMC). These cells are the same cells that are used in bone marrow transplantation, they are not expanded or manipulated stem cells, just cells from the bone marrow that have been depleted of red blood cells. In other mice the scientists injected a control solution of phosphate buffered saline. All injections were performed intravenously.
The injected bone marrow cells were found to accumulate near the area of brain injury. Blood vessel cells, termed endothelial cells, were found to start multiplying near the area of injury in animals that received BMMC but not control animals. Multiplication of endothelial cells is viewed as a sign of new blood vessel formation, called “angiogenesis”. The process of angiogenesis is usually involved in healing of tissue, or generation of new tissue to replace damaged tissue. Thus this suggests that the stem cells from the BMMC may be triggering the cellular microenvironment surrounding the brain tissue to start proliferating.
Indeed if the BMMC are stimulating a repair process, the next question is whether the BMMC are themselves forming new neural tissue, or if they are producing factors that stimulate resident stem cells in the brain to produce new brain tissue. When the investigators assessed the multiplication of endogenous brain stem cells, they found that these cells started to multiply. Furthermore, they found that multiplication of the endogenous brain stem cells is actually dependent on angiogenesis. Specifically, when the angiogenesis blocking molecule endostatin was given to mice that had received BMMC, the endogenous brain stem cells did not multiple. Multiplication of these cells was associated with functional recovery of the animals as assessed by behavioural testing.
There are several “closed system” devices that allow for the harvesting of the bone marrow, isolation of BMMC and reimplantation. The fact that this study shows intravenous injection of BMMC induces some therapeutic benefit should trigger further investigations in the clinical setting. Previously it was required to have a fully equipped laboratory to perform such clinical trials. Now devices like Harvest Technology’s BMAC system, Arteriocyte’s Magellan System, or Bio-Met’s GPS system all should facilitate doctors to perform such clinical experiments.

Filed Under: News, Stem Cell Research, Stroke Tagged With: , , , , ,
April 29, 2011 by

Stem Cell trial volunteers thank doctors at reunion lunch

Miami Herald, by Fred Tasker, ftasker@MiamiHerald.com
Stem cell therapy was originally used for the treatment of leukemias in the form of bone marrow transplant. Nearly 2 decades after this groundbreaking work, clinical trials initiated using bone marrow stem cells for treatment of heart patients. Bone marrow stem cells possess the ability to stimulate new blood vessel formation, a process called angiogenesis, which is essential in: a) accelerating healing after a heart attack; and b) in patients who have angina, stimulating new blood vessels to grow and take over the function of the clogged arteries that are causing the angina.
Initial work in this area involved administering stem cells from the bone marrow that were non-purified, directly into the heart muscle. Subsequently new techniques were developed so that open heart surgery was not needed. These techniques include the use of catheter-based delivery systems. Additionally, scientists found that one type of stem cell that is found in the bone marrow, called the mesenchymal stem cells, is actually more potent than bone marrow non-purified cells. Clinical trials have been performed with mesenchymal stem cells for heart failure. One of the major ones involved intravenous administration of “universal donor” cells. This article describes some of the patients that participated in Osiris’ 51 patient clinical trial.
“I believe in miracles, God — and my doctors,” said Edgar Irastorza, 33, the youngest of 51 patients at the luncheon.
Early results are promising, says Hare, director of UM’s Interdisciplinary Stem Cell Institute.
“We don’t know what the results will be, but things are going well. The fact that you’re here is testament to that,” he told the patients, united for the first time at a luncheon titled “Heart of a Pioneer” to celebrate their struggle.
Irastorza, a Miami property manager, said he died briefly on Oct. 6, 2008. A genetic defect gave him such a serious heart attack that his heart stopped for a few minutes. Doctors who revived him said half his heart was dead and warned him to prepare for a short, disabled life. They wanted to insert a defibrillator into his chest.
“I didn’t want that,” he said. “I didn’t want to give up sex and dancing.”
On March 3, 2010, UM doctors used a catheter inserted through a slit in his groin to inject millions of tiny stem cells into his damaged heart.
At the Friday luncheon, Irastorza presented to the crowd a five-minute video of his new self, doing an energetic, head-spinning break dance.
“I’m not completely back to normal, but, compared to before, it’s night and day,” he said.

Felix Morales, 80, a retired agriculture worker, had a heart attack 25 years ago and recently had become too easily fatigued to take care of the collards and peppers and the mamey and mango trees in his Miami backyard.
A year ago, he got one of the stem-cell treatments. “It took a while, but I feel good right now,” he said. “I have no words to express my gratitude.”
Evangeline Gordon, 40, a state probation officer from Miami, called 911 one October night in 2009, thinking she had a bad gas attack. To her shock, doctors told her a heart attack had damaged 70 percent of her heart muscle. They began discussing a heart transplant.
Instead, she volunteered for the UM program and got stem cells from a donor. Like most of the others, she doesn’t know if she got real stem cells or a placebo treatment used for comparison.
“I’m up and down,” she said Friday. “I still get angina and fatigue, but I don’t feel like I’m going down anymore.”

Filed Under: Clinical Trials, News, Stem Cell Research, Stem Cell Therapy Tagged With: , , , , , ,
April 27, 2011 by

Forcing Stem Cells into Circulation Results in Protection from Liver Failure in Animals

Zhang et al. Toxicol Lett.
While previous studies showed that administration of bone marrow cells are capable of repairing livers in animal and human studies, relatively little work has been performed to augment existing means by which the body uses its own stem cells to heal the liver. Specifically, it has been demonstrated that in liver failure bone marrow stem cells exit the bone marrow and home to the damaged liver. While conventional approaches include performing a bone marrow aspiration and mechanically placing the bone marrow into the liver, usually vial the hepatic artery, an alternative would be administration of a chemical that “instructs” the bone marrow stem cells to exit the bone marrow and go into systemic circulation. The other approach would be to augment the chemical signals that the injured liver produces to attract stem cells. This approach is currently pursued in other indications by the company Juventas. Stromal Derived Factor (SDF)-1 is produced by injured tissues and induces migration of bone marrow stem cells. The genetic administration of SDF-1 into already injured tissues causes an increase in stem cell trafficking and has been demonstrated to augment existing regenerative mechanisms.
A recent study (Zhang et al. Granulocyte colony-stimulating factor treatment ameliorates liver injury and improves survival in rats with d-galactosamine-induced acute liver failure. Toxicol Lett. 2011 Apr 27) from the First Affiliated Hospital, School of Medicine, of the Xi’an Jiaotong University demonstrated that administration of the stem cell mobilizer G-CSF into rats with chemically induced liver failure results in prolonged survival and the appearance of liver regeneration.
The investigators administered a single dose of d-galactosamine (d-GalN, 1.4g/kg) to induce ALF. After 2h, the rats were randomized to receive G-CSF (50μg/kg/day), or saline vehicle injection for 5 days. In the liver failure model, 5-day survival after d-GalN injection was 33.3% (10/30), while G-CSF administration following d-GalN resulted in 53.3% (16/30) survival (p=0.027). G-CSF treated rats had lower ALT level and less hepatic injury compared with saline vehicle rats. The increases of CD34+ cells in bone marrow and liver tissue and Ki-67+ cells in liver tissue in G-CSF treated rats were higher than those in saline rats.
These data suggest the possibility that stem cell therapy using chemicals that mobilize endogenous stem cells may be useful in the treatment of liver failure. It remains to be seen whether other chemicals associated with mobilization may cause improved outcome. For example, in addition to G-CSF, agents such as M-CSF, GM-CSF, parathyroid hormone, and the CXCR4 antagonist Mozibile are all capable of inducing mobilization of different types of stem cells.

Filed Under: Adult Stem Cells, Liver, News, Stem Cell Research Tagged With: , , , ,
March 14, 2011 by

StemCells, Inc. Initiates World’s First Neural Stem Cell Trial In Spinal Cord Injury

StemCells Inc Press Release
StemCells Inc announced today they are initiating a clinical trial using their fetal derived neural progenitor cells for the treatment of spinal cord injuries. Previously the company had reported that their stem cells, called HuCNS-SC, are capable of differentiating into various neural lineage cells including neurons, oligodendrocytes, and astrocytes. The fact that HuCNS-SC are derived from fetal sources allows them to possess a lower ability to stimulate immune responses, therefore, the cells can be used as an “off the shelf” product.
According to the company “The Company’s preclinical research has shown that HuCNS-SC cells can be directly transplanted in the central nervous system (CNS) with no sign of tumor formation or adverse effects. Because the transplanted HuCNS-SC cells have been shown to engraft and survive long-term, this suggests the possibility of a durable clinical effect following a single transplantation. StemCells believes that HuCNS-SC cells may have broad therapeutic application for many diseases and disorders of the CNS, and to date has demonstrated human safety data from completed and ongoing studies of these cells in two fatal brain disorders in children.”
The proposed study will be conducted at the Balgrist University Hospital, in Zurich, which is a private, non-profit institution managed in accordance with economic principles. The clinic has three key areas of expertise: it is a highly specialised centre providing examination, treatment and rehabilitation opportunities to patients with serious musculoskeletal conditions; it is responsible for training future doctors studying at the University of Zurich in orthopaedics and paraplegiology and providing professional training for doctors and medical staff in the domains of orthopaedics, paraplegiology, rheumatology, anaesthesiology and radiology; it is a research centre dedicated to improving quality for healthcare in the future. The number of patients or inclusion/exclusion criteria for the trial was not mentioned in the press release. However a look at clinicaltrials.gov reveals the following:
The study is a 12 patient Phase I/II trial in which treated patients will also receive immune suppression so that the transplanted cells will not be rejected. The trial has the following inclusion/exclusion criteria:
Inclusion Criteria:
• T2-T11 thoracic spinal cord injury based on American Spinal Injury Association (ASIA) level determination by the principal investigator (PI)
• T2-T11 thoracic spinal cord injury as assessed by magnetic resonance imaging (MRI) and/or computerized tomography (CT)
• ASIA Impairment Scale (AIS) Grade A, B, or C
• Minimum of six weeks post injury for the initiation of screening
• Must have evidence of preserved conus function
• Must be at stable stage of medical recovery after injury
Exclusion Criteria:
• History of traumatic brain injury without recovery
• Penetrating spinal cord injury
• Evidence of spinal instability or persistent spinal stenosis and/or compression related to initial trauma
• Previous organ, tissue or bone marrow transplantation
• Previous participation in any gene transfer or cell transplant trial
• Current or prior malignancy
Success in treatment of spinal cord injury has been reported in the peer reviewed literature by Cellmedicine in which a patient was treated with a combination of cord blood hematopoietic and placental matrix mesenchymal stem cells http://www.intarchmed.com/content/pdf/1755-7682-3-30.pdf.
The advantage of the approach proposed by StemCells Inc is that only one injection of stem cells may be necessary . The disadvantage is that while the stem cells may generate neurons, it is difficult to imagine how one source of stem cells alone can recapitulate and accelerate the multicellular process involved in healing of the spinal cord.
Treatment of spinal cord injuries using stem cells is also underway by the company Geron who uses embryonic stem cell derived oligodendrocytes in patients with spinal cord injury.
Two previous trials have been reported in the area of spinal cord injury that used mesenchymal stem cells exclusively. In 2006 the group of Movilgia et al from Argentina treated two patients with spinal cord injury using an interesting protocol of T cell plus MSC. Forty-eight hours prior to NSC implant, patients received an i.v. infusion of 5 x 10(8) to 1 x 10(9) AT cells. NSC were infused via a feeding artery of the lesion site. Safety evaluations were performed everyday, from the day of the first infusion until 96 h after the second infusion. Patient 1 was a 19-year-old man who presented paraplegia at the eight thoracic vertebra (T8) with his sensitive level corresponding to his sixth thoracic metamere (T6). He received two AT-NSC treatments and neurorehabilitation for 6 months. At present his motor level corresponds to his first sacral metamere (S1) and his sensitive level to the fourth sacral metamere (S4). Patient 2 was a 21-year-old woman who had a lesion that extended from her third to her fifth cervical vertebrae (C3-C5). Prior to her first therapeutic cycle she had severe quadriplegia and her sensitive level corresponded to her second cervical metamere (C2). After 3 months of treatment her motor and sensitive levels reached her first and second thoracic metameres (T1-T2). No adverse events were detected in either patient (Moviglia, G.A., et al., Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy, 2006. 8(3): p. 202-9).
Pal et al from Stemeutics in India reported 30 patients with clinically complete SCI at cervical or thoracic levels were recruited and divided into two groups based on the duration of injury. Patients with <6 months of post-SCI were recruited into group 1 and patients with >6 months of post-SCI were included into group 2. Autologous BM was harvested from the iliac crest of SCI patients under local anesthesia and BM MSC were isolated and expanded ex vivo. BM MSC were tested for quality control, characterized for cell surface markers and transplanted back to the patient via lumbar puncture at a dose of 1 x 10(6) cells/kg body weight. Three patients had completed 3 years of follow-up post-BM MSC administration, 10 patients 2 years follow-up and 10 patients 1 year follow-up. Five patients have been lost to follow-up. None of the patients have reported any adverse events associated with BM MSC transplantation (Pal, R., et al., Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study. Cytotherapy, 2009. 11(7): p. 897-911)
A search of clinicaltrials.gov for ongoing trials using stem cells in patients with spinal cord injury reveals the following:
1. Cairo University is performing a Phase I/II trial in 80 patients with spinal cord injury who are receiving autologous bone marrow derived stem cells. The trial includes patients that are treated with stem cells and receive physical therapy versus patients receiving physical therapy alone. The trial has completed enrollment and recruited patients who had injury 8 months to 3 years before entering the trial.

2. RNL Bio from Korea is performing a Phase I study on 8 spinal cord injury patients who had their injuries more than two months before entering the study. The cells administered are 40 million autologous adipose derived cells, given intravenously. The trial enrollment is completed and the Principle Investigator is Dr. SangHan Kim, MD from the Anyang Sam Hospital.

3. International Stemcell Services Limited from India is doing a 12 patient Phase I/II trial administering autologous bone marrow into patients after spinal cord injury. The trial enrollment is completed and the Principle Investigator is Dr.Arvind Bhateja, from the Sita Bhateja Speciality Hospital.

4. TCA Biosciences from Louisiana is performing a 10 patient Phase I trial using autologous bone marrow mesenchymal stem cells. The trial enrollment is completed.

5. The Memorial Hermann Healthcare System is doing a study using autologous bone marrow cells in children aged 1-15 using autologous bone marrow cells. The study plans to enroll 10 patients.

6. The Hospital Sao Rafael from Brazil is doing a 10 patient study using autologous bone marrow in spinal cord injury patients.
This exploration of clinicaltrials.gov tells us that relatively little is being performed in terms of stem cell therapy for spinal cord injury. Given the success of Cellmedicine at treating this condition, it will be interesting to see the outcomes of the other ongoing trials.

Filed Under: Adult Stem Cells, Clinical Trials, Spinal Cord Injury, Stem Cell Research Tagged With: , , , ,
February 23, 2011 by

Stem Cell Technique Could Help Those With Fast-aging Disease

Washington Examiner

February 23, 2011

Hutchinson-Gilfod progeria syndrome is a fast-aging disease that is rare, has no cure, and is fatal. Children with this disease undergo rapid aging and generally do not live to their teens. It is caused by a single mutation of the LMNA gene, which results in a defect in the production of lamin A, a protein which is required to build the membranous shell around genetic material. The majority of children with Hutchinson-Gilford progeria die from complications pertaining to hardening of their blood vessels. Fortunately, this disease is very rare, as only 64 children in the world are known to have it, however due to the small number of patients suffering from this disease, there are very few opportunities to study it and thus form any type of treatment.

New technology has introduced a new possibility in the treatment of this progeria. In the past five years, scientists have begun using targeted retroviruses that selectively alter DNA in order to cause a regression of cells from the muscle or skin into their stem cell form, pluripotent stem cells. Pluripotent stem cells have the potential to form various different types of cells in the body, depending on where they are transplanted to.

The cells that were taken from the patients were regressed back to their pluripotent stem cell stage by a research team led by Juan Carlos Izpisua Belmonte and Guanghui Liu at the Salk Institute in La Jolla, California. The researchers found that after this regression, the cells from the patients no longer contained the information that corresponded to diseased cells. However, despite the absence of the mutation in the stem cell state, these cells would not necessarily be rid of the defect which sets the fate for the disease. The resetting of the cells does allow for the scientists to study the progression of the disease its beginning.

Liu’s lab is working on a technique that will fix the genetic mutation responsible for the progeria in hopes of developing a treatment or even a cure for the disease. “Hopefully our efforts will be useful to generate … [non-symptomatic] progeria cells and help those progeria patients in the near future,” he said.

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