After suffering a massive heart attack in October of last year, Priyaranjan Dasmunsi has been in New Delhi’s Apollo hospital, too weak to move. Now 64 years old, the former government Minister will be transported to Bonn, Germany where he will receive autologous adult stem cell therapy from October 18 to the 24th.

According to his wife, Deepa, "We are in touch with doctors through mail at a couple of institutes there that use stem cell treatment. They haven’t assured us anything, as it’s going to be on an experimental basis. But I’m hopeful. It’ll take me a couple of days to sort out things, and decide how we want to go about the whole thing."

Dasmunsi and his wife will be traveling to Bonn upon the recommendation of a doctor from Germany who examined Dasmunsi two months ago. As Deepa adds, "He told us that in Germany they do treat such patients using stem cells, but it is all experimentation, as final results can’t be predicted in such cases. At this stage, I am clinging on to every glimmer of hope coming from anywhere. I want my husband back, and I’m sure he will be back."

Beyond being removed from life-support in January of this year, Dasmunsi has failed to make noticeable improvement. As Deepa further explains, "We are in touch with people in India but weren’t convinced. The German doctors appeared to be more transparent in their approach; they will take cells from his body only and culture them for use in his treatment. We tried everything: Ayurveda, homeopathy and even Baba Ramdev came to visit him, but his condition remains the same." In reference to Baba Ramdev and his yoga asanas, Deepa adds, "His way of curing is through performing yoga, but my husband is lying in almost a paralysed state and couldn’t perform them."

The doctors in Germany will use exclusively autologous (in which the donor and recipient are the same person) adult stem cells to treat Dasmunsi. The case is a particularly high-profile one in India – a country which is already contributing significant advances to the stem cell field and attracting an increasing number of international stem cell companies who have found a welcoming and friendly environment in India’s governmental regulatory system, as well as a virtually limitless market potential in the world’s second most populous country and the world’s most populous democracy. Although stem cell entrepreneurship is booming in India, many of the latest advances have yet to be translated into clinically available therapies, however. The Dasmunsi case is now setting a new precedent and drawing increased attention throughout India to the regenerative properties of adult stem cells, and to the great promise that this new therapy holds when actually available in hospitals and clinics.

Fluidigm of San Francisco has announced the manufacture of a "specialized integrated fluidic circuit" that will "enable a variety of cell culture applications" in stem cell research.

The novel product, already commercially available, is expected to standardize and automate the stem cell culturing process, thereby significantly expediting stem cell research while lowering laboratory costs associated with such research. The most immediate application would be in iPS (induced pluripotent stem) cell technology.

According to Marc Unger, chief scientific officer of Fluidigm, "Reprogramming a patient’s differentiated cells, such as skin cells, into stem cells overcomes the inherent ethical and immunological barriers to therapeutic usage of embryonic stem cells. We believe our Stem Cell Culture Chip will be an enabling tool for stem cell researchers. By designing and building a stem cell-specific microfluid chip in conjunction with a complete support system, we can automate much of the mundane process steps and substantially reduce the complexity and cost of fundamental stem cell research."

Among its many characteristics, the Stem Cell Culture Chip and supporting instrumentation will allow for the seeding of chambers with stem cells, as well as automated methods for media exchange and dosing of cells with reagents under programmable control, all of which will be analyzable via time-lapse microscopy under fluorescent as well as transmitted light.

Based in San Francisco, Fluidigm specializes in the manufacture and commercialization of biologically integrated circuits, such as the Integrated Fluidic Circuit (IFC) systems technology – a proprietary platform which involves the miniaturization and integration of liquid-handling components on a single microfluidic device. As described on the company’s website, these IFC systems consist of instrumentation, software and single-use chips which "increase throughput, decrease costs and enhance sensitivity compared to conventional laboratory systems." As further described on the company’s website, "tens of thousands of fluid control valves and interconnected channels are fabricated within miniature devices. We call these devices integrated fluidic circuits (IFCs) because, like their analog in the semiconductor industry, they are networks of discrete pathways and intermediate switches. Instead of electrons, they move molecules of biological samples and reagents in a dazzling variety of patterns." As also stated on their website, "Fluidigm products have not been cleared or approved by the Food and Drug Administration for use as a diagnostic and are only available for research use."

With other similar products in its pipeline, Fluidigm represents a new scientific paradigm in which semiconductor integrated circuitry, nanotechnology, and living biological systems intersect.

Researchers at the Scripps Institute in San Diego have announced the successful reversal of a rare but fatal genetic disorder, cystinosis.

According to Dr. Stephanie Cherqui, assitant professor in the department of molecular and experimental medicine at Scripps, "After meeting the children who suffer from this disease, like an 18-year-old who has already had three kidney transplants, and the families who are desperately searching for help, our team is committed to moving toward a cure for cystinosis, a lysosomal storage disorder. This study is an important step toward that goal."

In the study, the Scripps scientists used adult stem cells derived from bone marrow to treat cystinosis in a mouse model. The results indicated an effective reversal of the cystine accumulation and consequent cascade of cell death that characterize the disease.

A natural byproduct of metabolism, cystine is usually discarded by the body in healthy individuals but is retained in cystinosis due to a genetic defect in the lysosomal cystine transporter. The subsequent accumulation of crystals in tissue throughout the body, especially in the kidneys and eyes, is especially damaging.

Although the disease is extremely rare – afflicting no more than 500 people in the U.S. and only 2,000 people worldwide – cystinosis is almost certainly fatal. Prior to stem cell technology, the only available treatment for the disease was cysteamine, which slows the progression of kidney degradation though it can neither reverse the overall progression of the disease nor can it prevent the inevitable end-stage kidney failure. Additionally, as Dr. Cherqui points out, "Cysteamine must be given every 6 hours, so children have to be woken up each night to take this drug, which has unpleasant side effects. So although there is a treatment, it is a difficult treatment that does not cure the disease."

With the use of autologous (in which the donor and recipient are the same person) adult stem cells derived from bone marrow, however, cystine levels dropped 80% in each organ, which is enough to prevent kidney dysfunction. Additionally, less cystine crystal deposition was found in the corneas, along with less bone demineralization and improved motor function. As Dr. Cherqui explains, "The results really surprised and encouraged us. Because the defect is present in every cell of the body, we did not expect a bone marrow stem cell transplant to be so widespread and effective."

As a doctoral student in France in 1998, Dr. Cherqui helped discover the gene involved in cystinosis. In 2000, she generated the mouse model of the disease that is now used to study cystinosis by specialists throughout the world.

The results of the study are expected to have far-reaching implications beyond cystinosis, with potential applications to other genetic diseases with systemic defects of a progressive nature.

The U.S. company Stem Cell Therapy International Inc. (SCII) today announced that it has agreed to litigation settlement terms with both the U.S.-based company Histostem-USA, and with the S. Korean company known as Histostem-Korea.

The terms of the agreement are contingent upon the close of an SCII and Histostem-Korea merger, to be forthcoming within the month. Specifically, the litigation agreement is contingent upon SCII acquiring no less than 90% of the total fully diluted equity of Histostem-Korea at the close of the merger.

As stated in the press release, "For the consideration provided by Histostem-USA, including but not limited to a waiver of claims and a general release, Histostem-Korea and SCII have agreed to pay Histostem-USA $100,000 in cash, which will be divided into three equal payments over a two year period; and seven and one half percent (7.50%) of the fully diluted total outstanding shares of SCII common stock following the close of the merger between Histostem-Korea and SCII. The management of Stem Cell Therapy International Inc. will continue to finalize a new merger agreement between SCII and Histostem-Korea in the next fifteen days."

According to Andrew Norstrud, CFO of SCII, "Over the past year, it has been very challenging to make significant progress in operations, obtain the necessary financing to execute our global strategy, and complete the merger while we were waiting for the final resolution in the Histostem-Korea litigation. We appreciate all of the investors who have continued to support SCII, and we look forward to completing this merger and obtaining the necessary financing to enable us to accelerate our strategic initiatives in the near future."

As further stated in the press release, SCII "plans to leverage Histostem-Korea’s technology to be the state-of-the-art conduit for bringing Asian adult stem cells into the U.S. for clinical trials and the treatment of conditions on which Americans spend billions of dollars annually. This is predicated on successful clinical trial results by Histostem-Korea for Male Pattern Baldness, Buerger’s Disease and other conditions, whose repository of over 80,000 cord blood units has consistently met the rigorous standards of the Korean FDA. This has made Histostem-Korea the largest repository of cord blood in the world, and one of the first to actually profit from sales of its own stem cell-derived products."

Based in Tampa, Florida, SCII is a regenerative medicine company that is "devoted to the treatment of patients with stem cell transplantation therapy as well as providing the supplies of biological solutions containing new lines of stem cell products," as described on their website. As further described on the company’s website, SCII uses a type of adult stem cell procedure which they refer to simply as "stem cell transplantation (SCT)", which is based exclusively upon adult stem cells and which, as they explain, "is a surgical procedure that has been used successfully for 70+ years as a treatment of many diseases for which modern medicine has had no therapy, or in which state-of-the-art therapies stopped being effective. A documented 5 million patients have been so treated worldwide to date, evidenced by over 120,000 publications in MEDLINE (see www.nlm.nih.gov) amongst others. SCT is approved for use by the German authorities and the EU."

AmStem International, a wholly owned subsidiary of SCII, is based in Northern California where it specializes is "biotherapeutic and cosmetic stem cell products".

Founded in 2000 and based in Seoul, S. Korea, Histostem houses the largest repository of cord blood stem cells in the world, from which the company has already treated more than 500 patients. The company currently has 56 full-time employees and 28 part-time employees, and an intellectual property portfolio that consists of 5 patents that have already been granted and 6 patents applications that are still pending.

(Please see the related news article on this website, entitled, "Leading U.S. and S. Korean Stem Cell Companies Announce Merger", dated September 25, 2009).

A number of media sources, including The New York Times, recently reported that Prochymal, the leading adult stem cell product manufactured by Osiris Therapeutics, has "failed" two late-stage clinical trials. The term "failed", however, is the direct result of a technicality in FDA definitions and requirements: namely, the FDA does not recognize subsets of patients who participate in clinical trials. In actuality, however, Prochymal yielded statistically significant, highly impressive data in the specific subset of patients to whom this novel therapy was targeted.

Currently under question are two clinical trials in which Prochymal was tested as a therapy for graft-versus-host disease (GvHD), and also for steroid-refractory GvHD. In the clinical trial for steroid-refractory GvHD, the patients who took Prochymal in combination with steroids were found to have a 45% overall response rate, which was less than the 46% response rate for those patients who took steroids in combination with a placebo.

In the other clinical trial, for regular, non-steroid-refractory GvHD, it was found that 35% of all patients who received Prochymal exhibited an improvement in the disease, which, when compared to the 30% of patients who improved in response to a placebo, is not statistically significant.

When one looks at specific subsets of patients within the clinical trials, however, the data are quite different. Specifically, for patients with a form of GvHD that targets the liver and gastrointestinal tract, there was, in fact, a statistically significant response rate in which dramatic improvements were observed. However, at this time the U.S. FDA (Food and Drug Administration) does not typically approve therapies that are found to benefit only specific subsets of patients. The Osiris clinical trial results therefore call into question the FDA rules, which many scientists and physicians believe should be updated and revised in this regard.

GvHD is a potentially fatal disease in which immune cells from transplanted bone marrow recognize the recipient’s body as foreign and attack it. Of all the various types and cases of GvHD, it is the liver, the gastrointestinal tract, and the skin which are most commonly affected. Not to recognize a subset of patients who show significant improvement specifically in the liver and the gastrointestinal tract, in direct response to Prochymal, is to ignore a therapy that could have the greatest benefit for the greatest number of people. It is just one more example, of many, of how the FDA’s outdated rules and regulations have no scientific applicability whatsoever to the new field of regenerative medicine. It is just one more instance that proves the urgent importance of revision and updating of FDA laws.

Until such a revision actually happens, however, FDA regulators – and therefore most members of the media – are calling the Prochymal trials a "failure". The critically important subset of patients who showed statistically significant improvement in their livers and gastrointestinal tracts, as a result of receiving Prochymal, might beg to differ, however.

In fact, 74% of patients in this particular subset achieved complete remission of the disease – an astonishing improvement. If complete remission in nearly three-fourths of all patients in a particular subset cannot be considered "statisticallly significant", nothing can. The fact that this particular "subset" of patients represents the largest group of patients with this particular disease, is also worthy of serious consideration. Still, however, as a matter of general policy, the FDA refuses to recognize patient subsets – and therefore complete remission of the disease in 74% of patients in this particular group is considered a "failure".

Additionally, in the trial for steroid-refractory GvHD, Prochymal was found to increase the survival rate in children from the usual 20% to 60%. The FDA won’t recognize that data either, and therefore this particular trial is also considered to be a "failure". Parents with children who suffer with this condition, and who could therefore benefit from Prochymal, should not be allowed to have Prochymal, according to the FDA.

Derived from allogeneic (in which the donor and recipient are not the same person) adult stem cells known as mesenchymal stem cells (MSCs) that are harvested from the bone marrow of healthy young adults and cultured in the laboratory, Prochymal is the flagship product of Osiris Therapeutics, the world’s leading adult stem cell company. With its powerful immunomodulatory properties, Prochymal has already been found in numerous other studies to reduce inflammation and regenerate damaged tissue, in addition to ameliorating the immune response.

According to Duane Nash, an analyst at Wedbush Morgan Securities, "Prochymal really is the company’s main platform, and if Prochymal doesn’t work here then people will worry that it will not work elsewhere." Whether or not Prochymal is judged to be a success or a failure, however, seems to depend more upon outdated FDA technicalities than upon actual patient improvement.

Currently Prochymal is also being evaluated in 5 other indications, which include Type I diabetes and acute myocardial infarction, among other maladies. In fact, this is not the first time that Prochymal has "failed" a study. In June of this year the product was expected to improve lung function in patients with COPD (chronic obstructive pulmonary disease), but again the greatest response was found only in a specific subset of patients. Additionally, in March of this year Prochymal was evaluated in a clinical trial of Crohn’s disease but the FDA halted the trial due to design flaws in the study. The trial has since been redesigned and is expected to resume later this year.

It has been estimated that approximately 4,000 people in the U.S. alone are diagnosed with GvHD each year. The market potential has been projected to be between $150 million and $250 million.

As an ABC News reporter commented, "The unmet medical need might also persuade the U.S. Food and Drug Administration to abandon its normal protocol and approve the drug based on an analysis of a subset of patients, even if it fails the main goal of its trial to show the required level of complete response and survival."

As JMP Securities analyst Charles Duncan further adds, "It is possible that if you have efficacy in a subset of patients that is meaningful, then the trial may be deemed a success. You may actually see the U.S. Food and Drug Administration approve it on the basis of a subset analysis," particularly in the case of the steroid-refractory GvHD patient population. According to Edward Tenthoff, analyst at Piper Jaffray, "We are more confident in the steroid refractory study because we really believe that these patients do not respond to steroids."

As the ABC News reporter additionally points out, "If approved in other indications, the drug could become a blockbuster, generating sales of more than a billion dollars." Mr. Nash agrees, adding, "The thought is that the other indications that Prochymal could work in could potentially bring in over a billion dollars a year."

As of June 30th of this year, Osiris reported $52 million in cash and investments, which is enough to fund operations through the initial commercialization of Prochymal.

Prochymal is the only stem cell product currently on the market which has been granted both Fast Track and Orphan status by both the U.S. FDA and the European Medicines Agency. The mesenchymal stem cells (MSCs) contained in Prochymal are obtained from the bone marrow of healthy adult donors and are specially formulated according to a proprietary process for intravenous infusion. Osiris is also developing another adult stem cell product, Chondrogen, which is currently in clinical trials for the treatment of osteoarthritis of the knee.

A leader in adult stem cell therapies, Osiris Therapeutics is focused on the development of products for the treatment of inflammatory, orthopedic and cardiovascular diseases. Osiris was founded in 1992, went public in 2006 and currently has 47 U.S. patents, each with one or more foreign counterparts. In November of last year, Osiris formed a strategic alliance with the biotech company Genzyme that was valued at over $1.3 billion. In 2007, the two companies were awarded a $224.7 million contract from the U.S. Department of Defense for the development of Prochymal in the treatment of radiation sickness.

Perhaps this recent discrepancy between dramatic patient improvement in Prochymal’s clinical trials and the FDA’s definitions of "success" or "failure" will inspire a re-evaluation at the FDA of its rules on patient subsets. In fact, perhaps this would be an excellent opportunity for the FDA to further re-evaluate the modern relevance and scientific justifiability – or, more correctly, the lack thereof – of its rules and regulations in general.

Scientists at Stanford University School of Medicine have discovered that adult stem cells derived from adipose (fat) tissue are more easily and quickly reprogrammable into iPS (induced pluripotent stem) cells than are the more commonly used fibroblast (skin) cells. The finding provides a potential new application for the numerous liposuction procedures that are performed throughout the U.S. each year.

According to Michael Longaker, M.D., a professor of surgery at Stanford and coauthor of the study, "We’ve identified a great natural resource." Indeed, he refers to "liposuction leftovers" as "liquid gold". As cardiologist and senior author of the paper, Joseph Wu, M.D., Ph.D., adds, "Thirty to forty percent of adults in this country are obese. Not only can we start with a lot of cells, we can reprogram them much more efficiently. Fibroblasts, or skin cells, must be grown in the lab for 3 weeks or more before they can be reprogrammed. But these cells from fat are ready to go right away."

The scientists also found that adipose cells are convertible into iPS cells without the need for mouse-derived feeder cells, thereby eliminating the risk of cross-species contamination that would render the cells ineligible for human clinical use.

As a number of previous, independently conducted studies have already demonstrated, adult stem cells derived from adipose tissue are highly versatile, not only for their ability to differentiate into a wide variety of tissue types, but also for the rich and abundant supply of natural growth factors that are found in adipose tissue, which are essential for maintaining the potency of stem cells. Due to the ease with which adipose-derived adult stem cells can differentiate into bone, cartilage and muscle, these cells have already been routinely used in clinical veterinary therapies for years by companies such as Vet-Stem in the U.S. and VetCell in the U.K., both of whom have already repeatedly published detailed accounts of the therapeutic value of adipose-derived adult stem cells in the medical literature.

These latest findings represent a collaboration between the Lucile Packard Children’s Hospital, where Dr. Longaker is director of surgical research, and two Stanford institutes, namely Stanford’s Stem Cell Biology and Regenerative Medicine Institute, where Dr. Longaker is deputy director, and the Cardiovascular Institute of Stanford, where Dr. Wu is assistant professor of cardiology and radiology.

According to Dr. Ning Sun, who participated in the research at the Stem Cell and Regenerative Medicine Institute, and in reference to adipose-derived adult stem cells, "These cells are not as far along on the differentiation pathway, so they’re easier to back up to an earlier state. They are more embryonic-like than fibroblasts, which take more effort to reprogram."

Ordinarily, iPS cells are derived from fibroblasts via 4 genes that are used for the reprogramming and which are known as Yamanaka factors, named after Dr. Shinya Yamanaka who first developed the technique. Adipose-derived adult stem cells express higher levels of 2 of these 4 reprogramming genes, and when all 4 genes are added to the cells, Dr. Longaker and his colleagues discovered that only 0.01% of the fibroblast cells become iPS cells, whereas 0.2% of the fat cells become iPS cells, which represents a 20-fold improvement in the process.

As a Stanford representative explained in the initial press release, "The new iPS cells passed the standard tests for pluripotency: they formed tumors called teratomas when injected into immunocompromised mice, and they could differentiate into cells from the 3 main tissue types in the body, including neurons, muscle and gut epithelium." In other words, the newly derived cells are not yet ready for clinical use, since the formation of teratomas (tumors) remains a disqualifying trait, albeit a formal requirement of pluripotency, by definition.

Nevertheless, as Dr. Longaker explains, "The idea of reprogramming a cell from your body to become anything your body needs is very exciting. The field now needs to move forward in ways that the Food and Drug Administration would approve – with cells that can be efficiently reprogrammed without the risk of cross-species contamination – and Stanford is an ideal place for that to happen."

As Dr. Wu further adds, "Imagine if we could isolate fat cells from a patient with some type of congenital cardiac disease. We could then differentiate them into cardiac cells, study how they respond to different drugs or stimuli and see how they compare to normal cells. This would be a great advance."

Even though actual clinical therapies from iPS cells still remain years away, the discovery offers a new application for the endless supplies of liposuctioned fat – with its rich latticework of adipose cells, collagen and growth factors – which would otherwise normally be discarded as medical waste in countries such as the U.S, where it has been estimated that approximately two-thirds of the population, or approximately 200 million people, are overweight.