Nov 1, 2007: Going by the research and commercialization efforts underway in the industry, it won’t be long before stem cell therapy would be commonplace. The next 10 years will see a number of initiatives in that direction. The first products in the cardiovascular, diabetes, neurological, and tissue and organ stem cell therapy are expected to enter the market between 2009 and 2013

• Earlier this year, in a hospital in Bangkok, the life of a two-year-old baby was saved when the pediatrician decided to use stem cells. The baby was suffering from a fatal disorder of the immune system known as bubble-boy disease and lived because of a transplant of umbilical cord blood.

  In May, this year, India-based Manipal Hospital announced a major breakthrough in the treatment of Parkinson’s disease using stem cell therapy. It presented the case of Andrew Kisana, a US national. The doctors at the hospital said that the patient’s bone marrow was harvested at the regenerative medicine department and the mesenchymal stem cells were injected into the part of the brain, which was affected because of Parkinson’s disease. Kisana received three injections. This was the first time such a major effort was attempted in India for treatment of Parkinson’s disease. Kisana was suffering from the degenerating disorder for 15 years. After undergoing intensive drug therapy, lesion and deep brain stimulation (DBS), he had come to Manipal Hospital.

  In 2007, the US stem cell therapies market earned over $25 million in revenues, reports a Millennium Research Group (MRG) study. This revenue came from only two orthopedic products available in the US—Osiris Therapeutics’ Osteocel and Blackstone Medical’s Trinity. It is expected that, in addition to these two products, the entry of other products will open up the stem cell therapies market globally, not just in the US. A number of companies such as Aastrom Biosciences, Advanced Cell Technologies, Arteriocyte, Blackstone Medical, Cytori Therapeutics, Geron, Harvest Technologies, International Stem Cell Corporation, Stem Cell Sciences, Mesoblast, Cytometrix and Osiris Therapeutics are working on the applications of stem cell therapies.

  However, the development of the market for stem cell therapies is primarily dependent on the success of clinical trials, regulatory approval, and public acceptance. The first products in the cardiovascular, diabetes, neurological, and tissue and organ stem cell therapy are expected to enter the market between 2009 and 2013. The MRG report forecasted that by 2017 about 90 products are likely to be available in the market.

  The prevalence of potentially treatable disorders, unmet medical needs, rising health care costs, growth in the ageing population, and the success of the first stem cell therapy products are driving this market upward through 2017. The market has everything going its way. However, the success of the stem cell therapies will depend on the political and public support, reports MRG.

  In the ensuing pages BioSpectrum brings you a ringside view of the developments in the stem cell industry:

   

If one were to start compiling who’s who of stem cell research the list would indeed be long. Considering the successes in animal studies and applications of stem cells many organizations, companies and institutes are undertaking research on stem cell therapies. Some of them are working on clinical studies for diseases such as Spinal Cord injury, Parkinson’s Diseases, Muscular Dystrophy, Diabetes and Ischemic Heart Disease. There are over 600 stem cell trials currently listed on www.clinicaltrials.gov. And according to industry estimates, across the globe over 9,000 stem cell transplantations are conducted every year.

The human stem cell research has enormous potential for contributing to the understanding of human biology. Although it is not possible to predict the outcomes from the basic research studies, it offers real possibility for treatments and ultimately for cures for many diseases for which adequate therapies do not exist. There already exists evidence from animal studies that stem cells can be made to differentiate into cells of choice and that these cells will act appropriately in their transplanted environment.

Across the globe companies such as Aastrom Biosciences, Advanced Cell Technologies, Arteriocyte, Blackstone Medical, Cytori Therapeutics, Curis, Insception, Macropore, Geron, Harvest Technologies, International Stem Cell Corporation, Stem Cell Sciences, Stem Cell Technologies, Stem Cell Therapeutics, StemCells, Mesoblast, Cytometrix, Reneuron, CyGenics, Osiris Therapeutics and ViaCell are working on stem cell therapies. But so far only a few companies have been able to develop therapies that actually reached the clinical stage, while others are still making efforts to arrive at suitable therapies. Let’s look at what these stem cell research companies have been doing.

US-based Osiris Therapeutics, has been developing cellular therapies based on stem cells isolated from readily available adult bone marrow. These stem cells offer the opportunity to provide revolutionary treatments for many disease conditions. Currently, it has three product candidates in clinical trials. Prochymal is now enrolling patients in two phase III clinical trials. The first trial is evaluating the use of Prochymal to treat Graft versus Host Disease (GVHD), a life threatening disease afflicting patients who have received a bone marrow transplant. The second trial is evaluating Prochymal for the treatment of Crohn’s disease, a painful, disabling bowel disease that often leads to surgery. Provacel, a formulation of stem cells to repair damaged heart tissue following heart attack, completed enrolment of a phase I clinical trial. Osiris has also completed enrolment of a phase I/II study for its third product candidate—Chondrogen, an injection of stem cells formulated to repair damaged tissue in the knee joint and prevent the progression of arthritis.

US-based Blackstone Medical is dedicated to advancing techniques in the treatment of the human spine by identifying solutions with the spine surgeon and together creating pathways for innovative products. Through a partnership with Osiris Therapeutics, it distributes Trinity, a surgery-ready, first-of-its-kind bone graft product containing viable adult stem cells. Trinity is unique in the field of biologics because it provides all three bone growth properties: osteoconductivity, osteoinductivity and osteogenesis and is free of donor matching or recipient immune expression concerns. It is also a safe alternative to autograft harvesting because it eliminates patient discomfort and the risk of inherent complication as well as reducing procedure time.

Geron Corporation from the US has demonstrated that human embryonic stem cell (hESC)-derived cardiomyocytes improve heart function when transplanted after a myocardial infarction. This study is the first to document the potential clinical utility of regenerating damaged heart muscle by injecting hESC-derived cardiomyocytes directly into the site of the infarct. In addition, the research confirms the effectiveness of a scalable production system that enables Geron to manufacture the cardiomyocytes for use in ongoing large animal studies and, ultimately, testing in humans. The study describes the feeder- and serum-free, scalable production of hESC-derived cardiomyocytes, their survival in the infarct zone of rats when transplanted four days after infarction, and echocardiographic and MRI evidence of significant improvement in cardiac structure and contractile function.

Commercializing a unique population of adult stem cells for orthopaedic applications, Australia-based Mesoblast is conducting a phase 1b clinical trial at The Royal Melbourne Hospital in patients suffering from non-healing, long bone fractures. Interim results indicated strong bone regeneration and fracture union in every one of the first five patients implanted with Mesoblast’s proprietary cells. The success of the stem cell therapy in these patients eliminated the need for a second operation to harvest bone from their hips. There have been no reported cell-related adverse events. The success of this trial will lead to Mesoblast developing a proprietary stem cell product for repair of long bone fractures.

MNC biotech major Stem Cell Sciences focused on technologies to grow, differentiate, and purify embryonic and neural stem cells has a portfolio of patents and patent applications in both adult and embryonic stem cell fields. These include technologies to permit the generation of highly purified stem cells and their differentiated progeny for use in genetic, pharmacological and toxicological screens. Moreover, these technologies can be utilized to provide pure populations of appropriate cell types for transplantation therapies. It has an exclusive in-licensing of a technology, which is expected to significantly accelerate the application of human embryonic stem cells in both research and cell-based therapies. This discovery overcomes the key challenge in the effective scale-up of stem cell technologies—cell death.  The discovery, made by Prof Yoshiki Sasai’s team at The Institute of Physical and Chemical Research of the RIKEN Centre for Developmental Biology (Kobe, Japan), uses a class of compounds known as ROCK (Rho-associated kinase) inhibitors to block the onset of stem cell death when the clusters of growing cells are dissociated for transfer and scale-up. This discovery was effective on all human embryonic stem cell lines tested. The discovery represents a world’s first in terms of stem cell technology. Stem Cell Sciences has secured exclusive rights to the discovery in all global territories except Japan where the company holds non-exclusive rights.

Singapore-based Stem Cell Technologies is focusing on human adult progenitor cells derived from adipose tissue. Its team has optimized the isolation protocols for maximising the yield of Adipose Derived Adult Progenitor (ADAP) cells. It is in the process of charactering these cells as well as differentiating them along the various lineage pathways.

US-based Cytomatrix is a development stage biotechnology company focused on researching, developing and commercializing new therapeutics based on the use of cells to help treat diseases. It develops high value production devices. Its core technology is a unique cell growth technology termed “The Cytomatrix” that enables cells to grow in three dimensions. Its initial focus is on diseases in which hematopoietic (blood) cells such as stem cells and lymphocytes play a role. Made from inert materials through a sophisticated manufacturing process, the Cytomatrix provides an ideal environment for growing cells outside the body and for subsequent implantation into the body.

Australia-based adult stem cell research company, CyGenics is involved in developing new stem cell-based medical therapies. It is involved in the production of human T cells, a critical component of the immune system. The human T cell has implications in treatments for cancers, immune disorders, viral or bacterial infections and other conditions that are proving drug resistant. CyGenics is making efforts to develop stem cell-based treatments for wider range of medical conditions.