Over the last decade or so, I have observed a tempering of what was once a large and growing interest in stem cell therapies by patients, physicians and investors. I believe this dampening of enthusiasm has occurred as the public has awakened to some of the realities surrounding the logistics of the mass production, regulatory approval and eventual administration of living cells into people. Overall, the stem cell industry may be deserving of this love-hate relationship, and the stem cell products that are closest to approval right now aren’t actually stem cells at all.
In February 2004, Dr. Woo Suk Hwang of South Korea announced he had derived stem cells from a cloned human embryo, an achievement that earned him the reputation as a national treasure in South Korea and the “king of cloning” throughout the world. Despite Hwang’s subsequent disgrace and conviction for falsifying data, the damage had been done. Joe Q. Public believed the ability to regenerate organs from stem cells was right around the corner.
These events signaled the controversial popularity surrounding embryonic stem cells (ESCs), the harvesting of which involves the destruction of embryos. U.S. President George W. Bush’s restrictions on research involving ESCs—combined with the opinions of organizations such as the Catholic Church—had a chilling effect but could not contain the public’s interest and misconceptions that ESCs could regenerate entire organs such as hearts and livers.
In 2009, Geron Corporation, a U.S. public company that was developing a stem cell therapy for the treatment of spinal cord injuries, enjoyed a market value in excess of $1 billion. However, three years later, Geron announced they were exiting the stem cell market. That move was one of the most significant blows to the stem cell industry and a wake-up call for Joe Q.
Geron stated this decision was made after a “strategic review of the costs, value inflection timelines and clinical, manufacturing and regulatory complexities” associated with pursuing the continued research and development of ESCs. I would emphasize the regulatory complexities part of this statement. Geron’s Investigational New Drug (IND) application totaled 21,000 pages, a significant amount of which was devoted to addressing regulators’ concerns about approving ESCs, which were known to form tumors (teratomas).
Obscured in the shadow of the ESCs popularity, preclinical and clinical work was being conducted on its stepchild, the adult mesenchymal stem cell (MSCs). MSCs come under a variety of names such as mesenchymal stromal cells, mesenchymal precursor cells and mesenchymal-like stromal cells. Adult MSCs harbor no ethical controversies, as the procurement of these cells does not entail destroying the embryo. MSCs can be obtained from several different sources such as bone marrow, adipose tissue, the placenta and menstrual fluid. Additionally, MSCs can be obtained from the patient (autologous) or from a source other than the patient (allogeneic).
Several entities are attempting to commercialize their particular MSC and are represented by companies such as Mesoblast Ltd., Athersys Inc., Aastrom Biosciences Inc., Osiris Therapeutics Inc., Pluristem Therapeutics Inc., Medistem Inc., Cytori Therapeutics Inc. and TiGenix NV. All of these companies are allogeneic-based other than Aastrom and Cytori, which are autologous-based companies. Autologous-based therapies exploit a business model that is not intended to supply cells for the general population, as allogeneic therapy is potentially able to provide. Although still believed to fulfill a niche, the popularity of the autologous personalized-medicine approach has softened since the discovery that allogeneic MSCs are immunoprivileged and can be administered to patients without histocompatibility matching.
Interestingly, the mechanism of action of MSCs is not one of differentiation into tissue and organs. Instead these cells act as drug delivery devices. They respond to signals from injured tissue by secreting a cocktail of anti-inflammatory, angiogenic and cytoprotective therapeutic proteins that exert their pharmacologic effects on the injured tissue. Therefore, if you define a stem cell as an unspecialized cell that gives rise to differentiated cells, then the vast majority of MSCs currently in clinical trials should not rightfully be called “stem” cells.
Regardless of whether they are categorized as stem cells or not, allogeneic MSCs have emerged as the regenerative medicine industry’s best chance of developing commercial products over the near term. This is the unrecognized potential of cell therapy. Although ESCs were once the king, allogeneic MSCs have now taken over the throne.
Allogeneic cell therapy products are already being marketed for graft-versus-host-disease, a complication of bone marrow transplantation, and diabetic ulcers. More importantly, allogeneic MSCs therapies currently in Phase 2 or 3 clinical trials for degenerative indications that include rheumatoid arthritis, inflammatory bowel disease, diabetes, emphysema, ischemic heart disease, congestive heart failure, osteoarthritis, ischemic stroke, peripheral artery disease, bone marrow transplantation and muscle injury.
Examining these indications reveal why allogeneic MSC-related products will be the reason the regenerative medicine industry should be highly successful in the future. These products could be game changers in that they have the potential to significantly modify ischemic and degenerative diseases where the current relief enjoyed today by patients is only symptomatic.
William R. Prather RPh, MD, is a registered oharmacist as well as a board certified internist and geriatrician. Prather received his BS in Pharmacy (1970) and his MD (1973) from the University of Missouri. He practiced internal medicine in the Kansas City, Miss. and Vail, Colo. areas until leaving internal medicine in 1987 to pursue a fellowship in geriatric medicine at Harvard University. He completed this fellowship in 1989.
In 1992 Prather left the practice of medicine to pursue a career in the financial industry where he has held senior healthcare research positions for a variety of investment banks. Prather co-founded Panacos Inc., a public pharmaceutical company. Additionally, he has been on the boards of several public and private companies, including Boston Biomedica Inc., a public medical diagnostics company; PriMed, a private medical device company; MdBio, a Maryland healthcare venture firm; and sat on the advisory board of MDS Capital Management, a Canadian venture firm.