January 25, 2012 by

Bone Marrow Stem Cells Significantly Improve Cardiac Mortality Rate in Heart Disease Patients

Texas Heart Institute researcher, Emerson Perin MD, PhD revealed that heart patients who were treated with bone marrow-derived adult stem cells died at a significantly lower rate that those who did not receive stem cells. Dr. Perin’s scientific findings represent yet another positive step in the ongoing fight against heart disease.

Dr. Perin is the Director of Clinical Research for Cardiovascular Medicine and Medical Director for the Stem Cell Institute at the Texas Heart Institute in Houston, Texas. Dr. Perin’s study showed that patients treated with stem cells were 90% less likes to die from an adverse cardiac event than patients who were not treated with stem cells.

“We obtained remarkable results from our study in which we injected stem cells derived from the bone marrow of a healthy donor into patients with heart failure. Heart function and exercise capacity improved in some cell-treated patients. Most importantly, cell therapy significantly reduced cardiac adverse events, including death. Three of 15 (20%) control patients died of cardiac causes, whereas only 1 of 45 (2%) cell-treated patients had a cardiac-related death. Despite the small numbers, our findings showed that cell therapy significantly improved cardiac mortality,” said Dr. Perin.

Filed Under: Adult Stem Cells, Heart Disease, News, Stem Cell Research Tagged With: , , ,
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: , , , , ,
January 12, 2012 by

Excerpts from Interview with Dr. Amit Patel, Director of Regenerative Medicine, University of Utah by Thomas Ichim, Ph.D, CEO of Medistem Inc

www.thelatestwith.com

Ichim: Which one was the first stem cell trial for cardiac conditions?

Patel: It is like one of those questions like who did the first heart operation. There is a lot of debate as to what was the first to use cells plus therapy and there have been a number of trials. Myoblasts were performed in 2000, the Chinese reported work performed in 1999 or 2000, and the Ralfstock guys in Germany 2000s. So there are a number of trials, including ours, all in the 2000-2003 period that where being conducted almost simultaneously.

Ichim: Pardon me for asking because I should really know this, which one was yours?

Patel: The original CABG plus cells, which was performed in South America and India.

Ichim: Lets talk about Phase 2 trials in cardiac, we all have seen the excellent co-development deal between Cephalon and Mesoblast that happened in December of last year and we are all interested in how far are they?

Patel: The Cephalon-Mesoblast work is interesting. They are doing a 60 patient randomized trial here in the US in patients with Class II-IV heart failure. From the data thus far released there is a significant reduction in treatment group in terms of adverse events as compared to the placebo control group, they have not reported any efficacy data in terms of ejection fraction and the like.

Something unique from the data they presented was that they showed up to 2/3 of the control group were class III heart failure and 2/3 of the treatment group were class II. The early data was very interesting and promising. The safety of the data was very eloquent and reproducible. One thing that was very unique was Erik Dukker’s European large animal acute MI data which was the best in terms of scar reduction for any allogeneic MSC that I have seen to date. That data, if it pans out, in humans will be very interesting.

Ichim: How did Mesoblast administer their cells? Did they use balloon catheter in the heart failure patients?

Patel: They used NOGA mapping and administration, in chronic heart failure, both ischemic and non-ischemia. They did not do acute myocardial infarction in this trial.

Their trial had similarities with our Phase II Aastrom, which also uses NOGA administration in treatment of patients with ischemic and non ischemic heart failure. It is different in that we were looking only at class III/IV heart failure.

Ichim: How is that trial coming along?

Patel: Ours is completed from the patient recruitment and treatment perspective.

We are waiting 6 month data. Our trial was a three center trial between myself, Tim Henry and Mark O’Costa. These three centers were heavy enrollers. We had low adverse events so far. This study involves patient’s own bone marrow stem cells expanded for 12 days using Aastrom’s proprietary bioreactor system.

Ichim: Lets go back to my question about Mesoblast. Remember we were chatting at the meeting about this. There seems to be a lot of different players in this field that are all using bone marrow derived stem cells. Obviously I believe endometrial derived stem cells possess numerous advantages. But there is Osiris’s mesenchymals, there is Athersys who are using Catherine Verfaille’s cells that seem to be like mesenchymal stem cells except for their smaller size. What is the cell that Mesoblast is using? Are they just another type of mesenchymal stem cell?

Patel: By name they call them the cells mesenchymal precursors. The Mesoblast cells are unique in that they express STRO-1 and VLA-4.

In my opinion everyone’s stem cells have unique properties and surface markers be they Osiris, Mesoblast, Athersys, Allocure, and a couple other products that are bone marrow based.

What is unique to see will be the IP landscape, are they same cells or cousins? This may be a situation like the CD133 versus CD34. In this field we know that all mesenchymal stem cells are not the same but the question will be how similar or different are they when you apply them clinically?

Ichim: Did we forget to mention any other ones?

Patel: I am sure that we did, but not for want to miss them but just because they have not made enough noise. Actually the one trial we forgot to discuss was the Athersys phase I which Warren Sherman from Columbia presented using the Cricket catheter, which is adventitial delivery, that was a very safe trial. It will be interesting to see how they do in the next generation for their phase II AMI study.

Ichim: That was very interesting. That was the one with the bizarre catheter that actually had a couple of needles in it?

Patel: That catheter had one needle, it causes a microperforation to allow for perivascular injection. This is a very innovative concept since people that use the standard intracoronary delivery techniques seem to have a lot of washout of the cells.

Ichim: I don’t get it. So they are making a small hole in the blood vessel, why is it that there is no bleeding or damage?

Patel: The microperforation is way too small. You do not perforate into the pericardium. It only barely perforates. However it does require a well highly trained skill set to manipulate that catheter. If you had been listening to Dr. Sherman’s presentation you would have seen that there were no catheter-related injuries.

Ichim: (Laughing). OK, what about the large Brazilian data? That was also a session that I didn’t listen through in entirety.

Patel: That data was 10 year follow-up on several Brazilian studies. The work was initially performed in heart failure using NOGA by Hans Doneman, then they had Emerson Perin and Jim Willerson. We also had our work which involved CABG. That was groundbreaking work that set the foundations for a lot of the cardiac cell therapy that is being performed today. We are still waiting to hear the outcomes of the studies that were funded by the government of Brazil including the work on Chagas, dilated cardiomyopathy, and CABG.

Ichim: Speaking of South America, what did Jorge Tuma present?

Patel: This was incredible data that had patients who have been followed for 8 years. Cell administration was performed via the retrograde technique which we developed with him. The original experiments involved bone marrow mononuclear cells isolated by ficoll, heap-starch, CD34, etc, he is now using the Harvest system for autologous bone marrow mononuclear cell collection. He presented data on ten patients treated with this.

Ichim: This is what I love about interviews, I can ask all sorts of questions about things that I should know but I don’t. What exactly is this “retrograde technique”? I have heard you mention it several times.

Patel: We access the venous system of the heart. We occlude the outflow and deliver the biologic into the heart. What is unique is that the venous system does not get the same atherosclerosis as the arterial system. This procedure has been around since 1898..its been around from back then…the idea was can we give oxygenated blood back to the heart. It was in the 50s and 60s when Illahi started to implement this. I use this in my heart operations to give chemicals and nutrients into the heart backwards during open heart operations…so I said how

Administration of cells using the retrograde technique takes me half hour to do. This appears to be a safe and cost efficient means to deliver a biologic to the heart on incredibly sick patients.

Ichim: To put in things in perspective regarding cell administration. I know that NOGA is expensive and not too many centers have it. But how long does it take to do a NOGA administration of stem cells into the heart?

Patel: 1-2.5 hours, usually 90 minutes at best, you are manipulating the inside of the heart so there is a risk of irregular rhtyums, also low risk of perforation

Ichim: I still don’t really understand this retrograde technique. How is it that the cells actually enter the heart? Do they actually cross into the tissue?

Patel: You block the outflow of the heart and under pressure you push the cells into the venous system. So you have created a column of cells. You have antegrade blood flow and retrograde stop flow, so the cells either go into the tissue or perforate the sinus…perforate the sinus is very rare, less than 1 % in over a couple hundred patients. These are microperforations in the venous system so it doesn’t require emergent surgery…all of the patients in which this has occurred have done well.

Juventas presented some data in large animals in which the SDF plasmid showed a significant uprgulation using retrograde techniques in contrast to other means of delivery.

Ichim: To switch topics I saw you on CNN about spraying stem cells on poor patients with bad burns, how do the cells go inside of the tissue?

Patel: We add calcium and thrombin, it looks like jello if you were to spray it into the petri disue, so you have retention by tissue adhesion and the mechanical properties of the collagen, thrombin and calcium, so you are creating a matrix for your biologic. So it really is spray on and it actually sticks there.

Ichim: I remember you now based in Utah, what ever happened to that company in your neck of the woods Allocure? How are they doing these days?

Patel: The last I heard they completed Phase I trial here in Utah, they were giving at the time of heart surgery for renal production. They have a bone marrow mesenchymal cell product. The trial is completed, we are looking to see what their next study will be. Will the stick to renal protection or will they follow other companies by entering CLI, heart failure, etc.

Ichim: You know, I was impressed by that company C3 or something like that, they were using differentiated cells for heart?

Patel: That was a Phase I/II trial by Joseph Bartnak where they have a bone marrow mesenchymal cell that was cultured in a procardiac cocktail. It was administered by noga or endocardial mapping. And again the data looked interesting…we look forward to their next trial and when they come to US

Ichim: What they were doing was really new in my humble opinion. It seems to me like everyone in this field is administering undifferentiated cells based on the belief or hope that the damaged tissue will program the undifferentiated stem cell to become a cardiomyocyte. To your knowledge are there other people using differentiated or semi-differentiated cells?

Patel: Yes of course. There is Capricor, Eduardo Marban’s company. They are taking a biopsy of the patient’s own heart, grow up the cells and put them back in. They don’t put the cardiospheres back in because they are too large but put in some cells derived from cardiosphere grown in vitro. One of the issues they are facing is that their procedure is very much dependent on the starting material. They were able to do biopsy but because there was large variability in the weight of the starting tissue, it is important to figure out how to get enough

Ichim: Conceptually it seems counter-intuative to take out heart from a patient with heart failure !

Patel: People do right heart biopsy in transplant patients, doing native heart biopsy you are always concerned about damaging the valve. Raj who was doing the procedure for them is a great interventionalist, but have to make sure that the procedure is designed so that other interventionalists who may not have his skill set can do it. The concept is great but manufacturing and reproducibility is important.

Filed Under: News Tagged With: , , , , , , ,
January 6, 2012 by

Stem Cells May Reverse Age-Related Multiple Sclerosis Effects

Proof-of-principle study provides hope for stimulating remyelination

Scientists at Joslin Diabetes Center, Harvard University, and the University of Cambridge have found that the age-related impairment of the body’s ability to replace protective myelin sheaths, which normally surround nerve fibers and allow them to send signals properly, may be reversible, offering new hope that therapeutic strategies aimed at restoring efficient regeneration can be effective in the central nervous system throughout life.

In a proof-of-principle study published in the journal Cell Stem Cell, the researchers report that defects in the regeneration of the myelin sheaths surrounding nerves, which are lost in diseases such as multiple sclerosis may be at least partially corrected following exposure of an old animal to the circulatory system of a young animal. Myelin is a fatty substance that protects nerves and aids in the quick transmission of signals between nerve cells.

Using a surgical technique, the researchers introduced an experimental demyelinating injury in the spinal cord of an old mouse, creating small areas of myelin loss, and then exposed those areas to cells found the blood of a young mouse. By doing so, they found that the influx of certain immune cells, called macrophages, from the young mouse helped resident stem cells restore effective remyelination in the old mouse’s spinal cord. This “rejuvenating” effect of young immune cells was mediated in part by the greater efficiency of the young cells in clearing away myelin debris created by the demyelinating injury. Prior studies have shown that this debris impedes the regeneration of myelin.

“Aging impairs regenerative potential in the central nervous system,” says author Amy J. Wagers, PhD, an associate professor of stem cell and regenerative biology at Harvard University and Joslin, who co-led the study with Professor Robin Franklin, director of the MS Society’s Cambridge Centre for Myelin Repair at the University of Cambridge. “This impairment can be reversed, however, suggesting that the eventual development of cell-based or drug-based interventions that mimic the rejuvenation signals found in our study could be used therapeutically.”

This could be particularly useful, she adds, in treating MS, which typically spans many decades of life, and thus is likely to be influenced by age-dependent reductions in the ability of myelin to regenerate. In MS, the body’s own immune system attacks the myelin sheath and prevents nerve fibers in the brain from sending signals properly, which can cause mild symptoms such as limb numbness or more serious ones like losing the ability to walk or speak. As people with MS age, remyelination decreases significantly, eventually causing permanent loss of nerve fibers.

“For MS sufferers,” says Franklin, “this means that, in theory, regenerative therapies will work throughout the duration of the disease. Specifically, it means that remyelination therapies do not need to be based on stem cell transplantation since the stem cells already present in the brain and spinal cord can be made to regenerate myelin, regardless of a person’s age.”

Other Joslin co-authors of the study were Tata Nageswara Rao and Jennifer L. Shadrach.

About Joslin Diabetes Center
Joslin Diabetes Center, located in Boston, Massachusetts, is the world’s preeminent diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School.

Filed Under: Multiple Sclerosis, Multiple Sclerosis, News, Stem Cell Research, Stem Cell Therapy 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 30, 2011 by

Bone Marrow Stem Cells Protect Lungs from Herbicide Injury

Yang et al. Clin Toxicol (Phila). 2011 Apr;49(4):298-302.
Paraquat is a herbicide that is linked to development of Parkinsons. It also is a toxin to lung cells and is used as a model of inducing lung injury in rats. In the current study the investigators wanted to see if administration of bone marrow mesenchymal stem cells had a therapeutic effect on paraquat-induced lung injury in rats.
The investigators used 54 female SD rats that were randomly divided into four groups:
a) Paraquat treated group,
b) Paraquat and bone marrow mesenchymal stem cell treated group,
c) Bone marrow mesenchymal stem cell alone treated group
d) Control untreated group
The stem cells were injected intravenously and animals were sacrificed 14 days after injection.
While animals receiving paraquat alone lived an averaty of 9.6 days, all rats receiving bone marrow mesenchymal stem cells lived more than 14 days. Bone marrow mesenchymal stem cell treatment was associated with less wet lung, decreases in plasma IL-1 and TNF-alpha, decrease in MDA, and decrease in NF-kappa B. Upregulated levels of the antioxidant enzyme superoxide dismutase was observed.
The ability to stimulate repair of the lung by mesenchymal stem cells is not new. Previous studies have shown that mesenchymal stem cells are capable of reducing endotoxin induced lung injury by secretion of keratinocyte growth factor. Other studies have shown that mesenchymal stem cells produce interleukin 1 receptor antagonist in the bleomycine induced model of lung fibrosis.
As with other stem cell therapies described on this website, there is some controversy as to the biological mechanisms by which the stem cells are mediating their therapeutic effect. One possibility is that they are secreting growth factors that stimulate proliferation of endogenous stem cells that are already resident in the lung. The other possibility is that the stem cells are directly differentiating into lung tissue.

Filed Under: Kidney and Lung, News, Stem Cell Research 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 12, 2011 by

Immune Cells Killing Stem Cells and Stem Cells Killing Immune Cells

Knight et al. J Neurol Sci.
Several studies have demonstrated that stem cells are useful in the treatment of multiple sclerosis. The Cellmedicine clinic published previously in collaboration with the University of California San Diego that 3 patients treated with their own fat derived stem cells entered remission. Other studies are ongoing, including a study at the Cleveland Clinic in which bone marrow stem cells differentiated into mesenchymal stem cells are being administered into patients with multiple sclerosis. Unfortunately the mechanisms by which therapeutic effects occur are still largely unknown. One general school of thought believes that stem cells are capable of differentiating into damaged brain cells. The other school of thought believes that stem cells are capable of producing numerous growth factors, called trophic factors, that mediate therapeutic activity of the stem cells. Yet another school of thought propagates the notion that stem cells are merely immune modulatory cells. Before continuing, it is important to point out that stem cell therapy for multiple sclerosis involving autologous hematopoietic transplants is different than what we are discussing here. Autologous (your own) hematopoietic stem cell therapy is not based on regenerating new tissues, but to achieve the objective of extracting cells from a patients, purifying blood making (hematopoietic) stem cells, destroying the immune system of the recipient so as to wipe out the multiple sclerosis causing T cells, and subsequently readministering the patient’s own cells in order to regenerate the immune system. This approach, which was made popular by Dr. Richard Burt from Northwestern University.
In order to assess mechanisms of how stem cells work in multiple sclerosis it is necessary to induce the disease in animals. The most widely used animal model of multiple sclerosis is the experimental allergic encephalomyelitis model. This disease is induced in female mice that are genetically bred to have a predisposition to autoimmunity. These animals are immunized with myelin basic protein or myelin oligodendrocyte protein. Both of these proteins are components of the myelin sheath that protects the axons. In multiple sclerosis immune attack occurs against components of the myelin sheath. Therefore immunizing predisposed animals to components of the myelin sheath induces a disease similar to multiple sclerosis. The EAE model has been critical in development of some of the currently used treatments for multiple sclerosis such as copaxone and interferon.
Original studies have demonstrated that administration of bone marrow derived mesenchymal stem cells protects mice from development of EAE. This protection was associated with regeneration on oligodendrocytes as well as shifts in immune response. Unfortunately these studies did not decipher whether the protective effects of the stem cells were mediated by immune modulation, regeneration, or a combination of both. Other studies have shown that MSC derived from adipose tissue had a similar effect. One interesting point of these studies was that the stem cell source used was of human origin and the recipient mice were immune competent. One would imagine that administration of human cells into a mouse would result in rapid rejection. This did not appear to be the case since the human cells were found to persist and also to differentiated into human neural tissues in the mouse. One mechanism for this “immune privilege” of MSC is believed to be their low expression of immune stimulatory molecules such as HLA antigens, costimulatory molecules (CD80/86) and cytokines capable of stimulating inflammatory responses such as IL-12. Besides not being seen by the immune system, it appears that MSC are involved in actively suppressing the immune system. In one study MSC were demonstrated to naturally home into lymph nodes subsequent to intravenous administration and “reprogram” T cells so as to suppress delayed type hypersensitive reactions. In those experiments scientists found that the mechanism of MSC-mediated immune inhibition was via secretion of nitric oxide. Other molecules that MSC use to suppress the immune system include soluble HLA-G, Leukemia Inhibitor Factor (LIF), IL-10, interleukin-1 receptor antagonist, and TGF-beta. MSC also indirectly suppress the immune system by secreting VEGF which blocks dendritic cell maturation and thus prevents activation of mature T cells.
While a lot of work has been performed investigating how MSC suppress the immune system, relatively little is known regarding if other types of stem cells, or immature cells, inhibit the immune system. This is very relevant because there are companies such as Stem Cells Inc that are using fetally-derived progenitor cells therapeutically in a universal donor fashion. There was a paper from an Israeli group demonstrating that neural progenitors administered into the EAE model have a therapeutic effect that is mediated through immune modulation, however, relatively little work has been performed identifying the cell-to-cell interactions that are associated with such immune modulation.
Recently a paper by Knight et al. Cross-talk between CD4(+) T-cells and neural stem/progenitor cells. Knight et al. J Neurol Sci. 2011 Apr 12 attempted to investigate the interaction between immune cells and neural stem cells and vice versa. The investigators developed an in vitro system in which neural stem cells were incubated with CD 4 cells of the Th1 (stimulators of cell mediated immunity), Th2 (stimulators of antibody mediated immunity) and Th17 (stimulators of inflammatory responses) subsets. In order to elucidate the impact of the death receptor (Fas) and its ligand (FasL), the mouse strains lpr and gld, respectively, were used.
The investigators showed that Th1 type CD4 cells were capable of directly killing neural stem cells in vitro. Killing appeared to be independent of Fas activation on the stem cells since gld derived T cells or lpr derived neural stem cells still participated in killing. Interestingly, neural stem cells were capable of stimulating cell death in Th1 and Th17 cells but not in the Th2 cells. Killing was contact dependent and appeared to be mediated by FasL expressed on the neural stem cells. This is interesting because some other studies have demonstrated that FasL found on hematopoietic stem cells appears to kill activated T cells. In the context of hematopoietic stem cells this phenomena may be used to explain clinical findings that transplanting high numbers of CD34 cells results in a higher engraftment, mediated in part by killing of recipient origin T cells.
The finding that neural stem cells express FasL and selectively kill inflammatory cells (Th1 and Th17) while sparing anti-inflammatory cells (Th2) indicates that the stem cells themselves may be therapeutic by exerting an immune modulatory effect. One thing that the study did not do is to see if differentiated neural stem cells would mediate the same effect. In other words, it is essentially to know if the general state of cell immaturity is associated with inhibition of inflammatory responses, or whether this is an activity specific to neurons. As mentioned above, previous studies have demonstrated that mesenchymal stem cells (MSC) are capable of eliciting immune modulation through a similar means. Specifically, MSC have been demonstrated to stimulate selective generation of T regulatory cells. This cell type was not evaluated in the current study, however some activities of Th2 cells are shared with Treg cells in that both are capable of suppressing T cytotoxic cell activation. In the context of explaining biological activities of stem cell therapy studies such as this one stimulate the believe that stem cells do not necessarily mediate their effects by replacing damaged cells, but by acting on the immune system. Theoretically, one of the reasons why immature cells are immune modulatory in the anti-inflammatory sense may be because inflammation is associated with oxidative stress. Oxidative stress is associated with mutations. Conceptually, the body would want to preferentially protect the genome of immature cells given that the more immature the cells are, the more potential they have for stimulation of cancer. Mature cells have a limited self renewal ability, whereas immature cells, given they have a higher potential for replication are more likely to accumulate genomic damage and neoplastically transform.

Filed Under: Adult Stem Cells, Multiple Sclerosis, Multiple Sclerosis, News, Stem Cell Research, Stem Cell Therapy Tagged With: , , , , , , , , , , , ,
March 31, 2011 by

AuxoCell Laboratories Licenses Umbilical Cord Tissue Stem Cell Service to PerkinElmer’s ViaCord

Viacord Press Release
Cord blood private banking involves storing your own cord blood mononuclear cells in case you need them later. Cord blood public banking involves banking the cells into a public pool so that if others need them, they have access to them. In some ways it seems like cord blood private banking is based more on hope than on reality. The majority of uses of cord blood are in leukemias. In patients with leukemia you need to use the cord blood of a related or unrelated donor, but rarely if ever do you want to use your own cord blood because it may have the leukemic mutations in it that caused the leukemia to appear in the first place. Therefore, the majority of cord blood banking is based on the belief that in the future the FDA will allow for procedures to take your banked cord blood, manipulate it to generate certain tissues in vitro and then reimplant those tissues back in you if you need them. There are of course exceptions to this. For example, there are clinical trials using your own cord blood for the treatment of cerebral palsy. Specifically, Georgia Health Sciences University is doing a 40 patient cord blood study in patients with cerebral palsy who have stored their own cord blood http://www.clinicaltrials.gov/ct2/show/NCT01072370. Additionally, Joanne Kurtzberg from Duke is performing an 120 patient study in children with cerebral palsy that have stored their own cord blood http://www.clinicaltrials.gov/ct2/show/NCT01147653. Other diseases are also being explored experimentally. Clinical trials are also being performed using patient’s own cord blood for type 1 diabetes. A group in Germany is doing a 10 patient trial http://www.clinicaltrials.gov/ct2/show/NCT00989547 and a group in Florida recently completed a 23 patient trial http://www.clinicaltrials.gov/ct2/show/NCT00305344.
Thus at present the field of private cord blood banking may have some very high future potential. Large companies are realizing this and accordingly are moving into this space. Perkin Elmers announced today that it has licensed technologies patented by AuxoCell Laboratories involving processing and storage of mesenchymal stem cells from the umbilical cord. As we discussed previously on the Cellmedicine website, the umbilical cord possesses mesenchymal stem cells that are in some ways more potent than bone marrow mesenchymal stem cells because they are more immature. The licensing of this technology will allow for Perkin Elmers to deliver to customers the ability to bank not only hematopoietic stem cells but also mesenchymal stem cells. There are many uses for mesenchymal stem cells. In fact numerous clinical trials have been performed using autologous mesenchymal stem cells for conditions ranging from heart failure, to graft versus host, to spinal cord injury.
“AuxoCell is pleased to partner with PerkinElmer’s ViaCord in offering umbilical cord tissue banking and expand our strategic partnerships to bring novel stem cell therapies from the bench to the bedside,” said Kyle Cetrulo, chief operating officer of AuxoCell Laboratories, Inc. “Partnering with ViaCord was an easy decision. They are the first family bank in the United States to freeze treatment-ready cord tissue stem cells upon arrival at the lab, which enables them to be ready for immediate use, if needed.”
“ViaCord is excited to offer another source of stem cells to our customers and believe we have found an excellent partner in AuxoCell. The agreement grants ViaCord’s customers exclusive access, in family banking, to expanding MSCs derived from cord tissue through AuxoCell’s elite patents,” said Morey Kraus, ViaCord’s chief scientific officer. “AuxoCell’s proprietary and validated manufacturing protocols will assist ViaCord in offering the very best in stem cell banking.”

Filed Under: Cord Blood Stem Cells, News, Stem Cell Research Tagged With: , , , , , ,
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