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: , , , , ,
October 21, 2011 by

Twins’ family coping with cerebral palsy

ASHLAND — Three-year-old twins with cerebral palsy are making life adventurous, challenging and bittersweet for the Hancock family.

“They’re happy kids but it definitely makes it more difficult because as a parent you want them to have every opportunity that every other child has,” said mother Carrie Hancock. “It’s hard, but we’re handling it the best we can.”

Because they were born 10 weeks premature, both children suffered developmental delays.

By the time Tessa and Dylan were 20 months old, Tessa had been diagnosed with cerebral palsy, a permanent disorder that affects movement and posture. At that time, parents Carrie and Jeremy were getting ready to take their daughter overseas for a stem cell transplant, a procedure that would allow Tessa to live a better, less physically restricted life.

In the midst of their planning, the family was soon faced with another obstacle. That January, Dylan also was diagnosed with cerebral palsy.

“What do you do? They’re your babies. You just go with it and do what you think is best,” Carrie said. “Before, we were always told that he just had developmental delays, but as much as you hated to hear it, it was almost a blessing because we were paying out of pocket for him because he hadn’t been officially diagnosed.

“That’s the silver lining I guess and now we’re able to get him the help he needs.”

The Ashland family ended up taking Tessa to Panama City, Panama, where she had her first round of stem cell treatments in 2009.

“She did really well and had a lot of improvement with her vision,” Carrie said. “Her tone in her hand had decreased and she wasn’t fisting all the time. When we went back in July, we took both the kids.”

The results were remarkable.

“As soon as we took him, he was like a whole other kid,” Carrie said of Dylan. “He was babbling and it helped him in so many different ways. He also just walked independently a couple months ago. For Tessa, it made her stronger. She was already smart and attentive.”

Today the twins attend therapy sessions at MedCentral Pediatric Therapy one day a week and preschool at Tri-County Preschool four days a week. They receive occupational, speech and physical therapy.

“A typical day for us includes them going to school a little after 8 and they’re picked up a little after 11,” Carrie said. “After we get them home and fed, Tessa goes down for a nap and then Dylan stays awake and I get alone time with him, which is nice. We work on walking and sitting up with them, but try to incorporate it into their play. We try to make it a fun time.”

The family takes the twins on outings by stroller and enjoy their play time together, but each day can be daunting.

“The biggest difference is the physical challenge of dressing and feeding. Tessa is in the process of being potty trained, but Dylan doesn’t want to yet,” Carrie said. “She can’t feed herself and we’re still changing diapers at age 3.

“Dylan’s not walking. If you ask him to pick up something, he doesn’t understand. It’s challenging.”

Recently, Dan and Stephanie Kreisher, of Ontario, held their third fundraiser for the family. Jeremy was on Dan’s 1994 state championship baseball team at Ontario High School.

The Kreishers and friends raised $1,400 for the Hancocks, along with providing them two iPads for Tessa and Dylan after learning the electronics would help their communication skills. The iPads were sponsored by Elite Excavating and Zara Construction.

“We have so much and are so fortunate that we wanted to help others,” Dan said. “Jeremy and Carrie are such positive people. They’re the happiest parents, just very admirable people.”

The feeling was mutual.

“I can’t say enough about Dan and Stephanie. The iPads are huge for us. We’re in the process of getting different communication devices to help with fine motor skills,” Carrie said. “They use them in school and it’s nice to be able to incorporate what they’re learning at home. Life isn’t easy, but we are very blessed.

“The best way to describe our family is that we’re taking the scenic route. We’re taking the back roads. We’ll get them there, but it just might take a little longer.”

Filed Under: Cerebral Palsy, News, Stem Cell Therapy 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: , , , , ,
May 27, 2011 by

Stem cell therapy gives dogs new pep in their step

Linda Goldston, lgoldston@mercurynews.com Mercury News
Cookie is a thirteen year-old Australian shepherd mix that has been having increasing trouble lying down and getting up. She could not walk down stairs and even during normal walks around the park her legs would give out. Cookie’s master, Ed Tani of Hayward was terrified that Cookie’s days were numbered. Ed then came across a revolutionary procedure for treating arthritic dogs called stem cell therapy. The treatment had been used with great success in horses for years, but more and more veterinarians are implementing the patented Vet-Stem Regenerative Cell therapy to their medical bag of tricks.
“This is an attempt to turn back time but without drugs,” said Brian Maxwell, a veterinarian whose specialty is orthopedic surgery at Adobe Animal Hospital in Los Altos, where Cookie’s joints were injected with her own stem cells this week.
The procedure of using stem cells to treat arthritis is based on the fact that stem cells have the ability to inhibit inflammation associated with arthritis, as well as to regenerate the injured cartilage. Vet-Stem uses stem cells derived from the fat tissue. Fat tissue contains stem cells that are called “mesenchymal” which are known to produce bone, cartilage, and other types of tissues. Additionally, mesenchymal stem cells also produce anti-inflammatory compounds such as interleukin-10.
Maxwell stated that “about 70 percent of the dogs treated show dramatic improvement; another 20 percent show moderate improvement”. Maxwell stated that of the 10 dogs that were treated so far, all but one of them improved. The dogs’ mobility was better and most of them were able to go off pain pills and anti-inflammatory medication, which can cause kidney and liver problems in many dogs.
“When she was 4 years old, she tore her ACL and had to have surgery,” said Wyle, a lecturer in Stanford University’s program in writing and rhetoric. “I thought, at that point, it was time to do it.”
The treatment of autologous fat stem cells have been performed by Vet-Stem since 2003. There have been numerous studies published by Vet-Stem regarding the treatment of dogs and horses using fat stem cells. For example in Black et al. Vet Ther. 2008 Fall;9(3):192-200, Dr. Harman’s group reported that “effectiveness of this therapy in dogs with chronic osteoarthritis of the humeroradial (elbow) joints and to determine the duration of effect. Fourteen dogs were recruited. Veterinarians assessed each dog for lameness, pain on manipulation, range of motion, and functional disability using a numeric rating scale at baseline and specified intervals up to 180 days after treatment. Statistically significant improvement in outcome measures was demonstrated.”

Filed Under: Adult Stem Cells, Arthritis, News, Stem Cell Research Tagged With: , , , ,
May 23, 2011 by

Bone Marrow Stem Cells Successful For Liver Failure Caused by Hepatitis B

Peng et al. Hepatology.
The liver is the most regenerative solid organ in the body. One can resect 2/3 of the liver and it will still regenerate back to normal size. There have been several experimental studies in animals where induction of liver injury is treated by administration of bone marrow stem cells. A video describing this may be seen at this link http://www.youtube.com/watch?v=XGdehdRApb0. Previous use of bone marrow cells in patients with liver failure has been described in a Japanese publication that is presented in this video http://www.youtube.com/watch?v=DdH6Mm4w98I.
A recent study Peng et al. Autologous bone mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: Short-term and long-term outcomes. Hepatology. 2011 May 23 from the 3rd Affiliated Hospital of Sun Yat-sen University, in GuangZhou, China reported outcomes of 53 patients with hepatitis B induced liver failure treated with 120 ml of their own bone marrow stem cells infused via the hepatic artery. These patients were compared to 105 control patients that were matched for age, gender, and liver enzymes. Additionally, the functional index of liver failure, the Model for End-Stage Liver Disease (MELD) score, was matched between the treated and control groups.
Bone marrow stem cells were isolated without complications. The cells were administered as a slow infusion into the hepatic artery. Given that hepatitis is associated with an increase in hepatic cancer, one of the concerns of bone marrow stem cell administration into this patient population is the theoretical possibility of accelerating tumor formation. This appeared not to be the case. Specificallyt, follow-up at 192 weeks post treatment revealed no differences in incidence of hepatocellular carcinoma (HCC) or mortality between the two groups. Additionally, there were no significant differences in the incidence of HCC or mortality between patients with and without cirrhosis in the transplantation group. In terms of efficacy, it appeared that 2 to 3 weeks after administration of bone marrow stem cells, the levels of ALB, TBIL, PT and the MELD score of patients who received stem cells were significantly improved as compared to control patients. Improvements where maintained in the majority of patients.
These data support the possibility of using autologous stem cells in the treatment of liver failure. One possible new and less invasive method would be to mobilize the existing stem cells of the patient by administering drugs such as G-CSF (Neupogen) that trigger entry of bone marrow stem cells into circulation. The therapeutic activity of stem cell mobilization was demonstrated by 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 who demonstrated that 5 day administration of G-CSF had therapeutic effects in the d-galactosamine-stimulated liver failure model.

Filed Under: Liver, News, Stem Cell Research Tagged With: , , , ,
May 22, 2011 by

Mimicking Human Diseases in Cells: iPS Cells Used to Create Model of Extremely Rare Condition Dyskeratosis Congenita

Batista et al. Nature.
Key to scientific progress is the ability to test new treatments in animals that represent the human disease of interest or in cells in the laboratory that represent the human disease. The better these test systems represent the human disease, the more likely it is that approaches successful in the test systems will actually work in the clinical trials. An example of test systems not being truly representative of human diseases are the animal models of cancer. Literally thousands of drugs, vaccines and other approaches have been demonstrated to cure cancer in mice, but when tested in humans do not work.
Stem cells are now being used to create in vitro (in the lab) models of human diseases. One way in which this is occurring is by creating stem cells from skin or other adult tissues of people with diseases. Specifically, the process of generating iPS cells allows for creation of cells that resemble embryonic stem cells from practically any adult tissue. Thus if one wanted to study drugs that affect lung function in patients with cystic fibrosis, one could take a small skin sample of a cystic fibrosis patient, generate iPS cells, and use these cells in vitro to create human lung tissue that would be similar to the lung of the original cystic fibrosis patient. This way one could take the artificially generated tissue and test drugs on it. Prior to the creation of iPS cells, something like this would have required taking out lung specimens from cystic fibrosis patients, something which would definitely not be ethical !
In the study discussed today (Batista et al. Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature. 2011 May 22) investigators studied the rare disease dyskeratosis congenita. This condition is associated with accelerated aging.
The study demonstrated that iPS cells from dyskeratosis congenita patients possess the exact same biochemical defects characteristic of the disease and when patients with different severity of the disease were used to generate iPS cells, the more advanced the disease was, the less telomerase activity was found in the cells.

Filed Under: News, Stem Cell Research Tagged With: , ,
May 13, 2011 by

Killing of the iPS Field?

Zhao et al. Nature.
Embryonic stem cells are associated with numerous ethical dilemmas. The creation of equivalents of ES cells through retrodifferentiation led to a new area of research that does not require destruction of life. Specifically, it was discovered that any adult cell can be transfected with several genes, which results in the cell taking the phenotype and function of cells that appear to be very similar to embryonic stem cells. These cells can give rise to any tissue that embryonic stem cells give rise to, and unfortunately, like embryonic stem cells for teratomas (tumors). We made a video to explain this http://www.youtube.com/watch?v=_RLlUdJLy74.
One of the most exciting medical properties of iPS cells is that they can be made from a donor and theoretically the cells and their differentiated offspring should not be rejected by the donor. This would allow for generation of compatible cells, without the need for immune suppression. However, a recent study suggests that this may not be the case.
In the study (Zhao et al. Immunogenicity of induced pluripotent stem cells. Nature. 2011 May 13) investigators assessed the ability of embryonic stem cells and induced pluripotent stem cells (iPS) to stimulate immune responses using inbred, genetically identical mice. They found that embryonic stem cells (ESCs) derived from C57BL/6 (B6) mice can efficiently form teratomas (an aggressive type of tumor) in B6 mice (syngeneic) without any evident immune rejection. However, when allogeneic ESCs from 129/SvJ mice where transplanted into B6 mice, they were rapidly rejected by the B6 immune system. This by itself is interesting because transplantation of adult stem cells, mesenchymal stem cells, does not lead to rejection when transplanted between mouse strains.
When B6 mouse embryonic fibroblasts (MEFs) were reprogrammed into iPSCs by either retroviral approach (ViPSCs) or a novel episomal approach (EiPSCs) that causes no genomic integration and transplanted into B6 mice rejection was observed. Specifically, the retrovirally-generated iPS cells were more immunogenic than those generated by the novel episomal method. Rejection of both types of iPS cells was characterized by T cell infiltration.
Global gene expression analysis of teratomas formed by B6 ESCs and EiPSCs demonstrated that several iPS genes were expressed that contributed to immunogenicity. According to the authors “these findings indicate that, in contrast to derivatives of ESCs, abnormal gene expression in some cells differentiated from iPSCs can induce T-cell-dependent immune response in syngeneic recipients.”

Filed Under: News, Stem Cell Research Tagged With: , , , ,
April 30, 2011 by

Where Cord Matrix Stem Cells Go After Injection

Maurya et al. World J Stem Cells. 2011 Apr 26;3(4):34-42.

Stem cell migration is a very relevant issue when discussing the systemic administration of stem cells as therapeutics. There is a widely held belief that intravenous administration of stem cells results in accumulation into the lungs and liver. While studies have demonstrated that stem cells home to area of injury, in part through the SDF-1 protein produced by injured tissue, relatively little work has been performed in terms of analyzing where stem cells home in healthy, or non-diseased situations. A recent study (Maurya et al. Non-random tissue distribution of human naïve umbilical cord matrix stem cells. World J Stem Cells. 2011 Apr 26;3(4):34-42) attempted to address this.
The scientists used human cord matrix mesenchymal stem cells. These cells are similar to the ones used by Osiris, except that some believe that they are more potent due to their relatively more immature origin. As a model system, the cells were injected into mice that lack an immune system due to a genetic mutation that causes lack of T cells and B cells (SCID). In order to track the human cord matrix stem cells, the cells were labeled with the radioactive tracer compound tritiated thymidine. This compound integrates into replicating DNA and is imaged using beta radiation detection.
The investigators assessed injected animals at days 1, 3, 7 and 14 for radioactivity. To confirm results they also used an immunofluorescence detection technique was employed in which anti-human mitochondrial antibody was used to identify human cells in mouse tissues. Additionally, standard microscopy and histology staining was performed.
The injected cord matrix mesenchymal cells preferentially accumulated in the lung 24 hours after injection. With time, the stem cells migrated to other tissues. Specifically, on day three, the spleen, stomach, and small and large intestines were the major accumulation sites. On day seven, a relatively large amount of radioactivity was detected in the adrenal gland, uterus, spleen, lung, and digestive tract. In addition, labeled cells had crossed the blood brain barrier by day 1.
The fact that injected stem cells enter various tissues in a healthy animal suggests the possibility that stem cells are involved in the natural renewal process. It would be interesting to see the same experiment was performed in the animal model of progeria if more stem cells would be integrated. Additionally, experiments should use allogeneic T cell reconstituted animals to see if allogeneic human cord matrix cells survive.

Filed Under: News, Stem Cell Research Tagged With: , , , ,
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