More than a decade ago, back in 2000, I collaborated on a project that brought together some of the world’s leading experts on tissue engineering. During a series of forums covering various topics, these world-class scientists presented groundbreaking research and described the therapeutic promise of innovations aimed at rebuilding fundamental tissue- and organ-level biologic functions. It was easy to be wowed by their tremendous achievements. These experts outlined potential cures for disease states that currently plague wide swaths of the population: regeneration of infarcted myocardium, transplantation of insulin producing cells, in vitro construction of viable liver tissue.
Yet, there was a measure of caution in the message. While the basic science was progressing at an impressive pace, major questions still remained, especially relative to cellular sources and signaling. Moreover, the pathway to commercialization was riddled with uncertainty and risk. What, exactly, is the product? And how should or will it be regulated?
Twelve years hence, a recent barrage of media coverage on tissue engineering breakthroughs led me to revisit these questions. Is tissue engineering, or, as it’s now more commonly referred to, regenerative medicine, ready to be translated into real therapies accessible to the broader-population of real patients? In this issue of FGA Index, I set off to find out.
Regenerative Medicine: From Bench to Bedside
In September The New York Times ran a three-part series featuring achievements in tissue engineering. The first two articles were essentially case studies—stories of individual patients undergoing experimental, one-of-a-kind treatments. The successes portrayed there seem nothing short of miraculous: transplantation of an artificial windpipe seeded with the patient’s own stem cells to replace one destroyed by cancer, regrowth of muscle tissue lost after an encounter with a roadside bomb in Afghanistan. The first patient was treated at Karolinska Institute in Stockholm and the second at the University of Pittsburgh’s McGowan Institute for Regenerative Medicine. The common denominator, of course, is that each received therapies conceived of and produced entirely within the confines of academic laboratories.
These individual cases clearly represent early-stage models: exceedingly expensive and complex experiments along the way to some future product. The “ultimate dream” driving these experiments, as Dr. Paolo Macchiarini of Karolinska notes, is to come-up with solutions that can viably meet the need of large volumes of patients—solutions such as drugs which prompt the body to rebuild its own tissues in vivo. Realistically, such solutions are a long way off. Even so, scientists learn more and more with each success, and each failure. And, as The Times’ stories illustrate, a handful of lucky patients benefit along the way.
The Regenerative Medicine Foundation projects the industry may top $10 billion within the decade. Indeed, according to Jaklenec et al, tissue engineering/stem cell sales have experienced a recent surge, with nearly 300% growth over the past 4 years to reach $3.5 billion. This represents a remarkable milestone for an industry that has been struggling to get off the ground for nearly 2 decades. As Robert Nerem notes in his excellent historical overview Regenerative Medicine: The Emergence of an Industry, private sector activity actually contracted in the early 2000s following a flurry of development—and corresponding hype—in the late 1990s. The downturn occurred not only as a consequence of a stagnant economy but also as a result of the sector’s failure to heed the need for new business models and fundamental infrastructure changes.
The challenges to commercialization of engineered tissues, especially cellular technologies, are many. In addition to finding the optimal cell sources and signals, there are issues of cell production, clinical development and regulatory pathways, standardization of manufacturing, and, finally, delivery mechanisms and reimbursement. Advancing this technology from bench to bedside hinges on a concerted effort by all stakeholders, including government, to facilitate product development pathways that can accommodate this breakthrough science. The regulatory landscape is presently evolving and FDA establishment of the Office of Combination Products and the Office of Cellular, Tissue and Gene Therapies promises to bring greater clarity to the validation process. Still, as Dusko Ilic observes in his summation of this year’s World Stem Cell Regenerative Medicine Congress, major hurdles remain in terms of creating better regulatory transparency, promoting strategies for obtaining reimbursement and educating clinicians, and in convincing investors and big pharma of the potential value of this emerging industry.
In the near term stakeholders and potential investors will be watching closely as more than 200 new therapies currently in the clinical trial pipeline make their way toward the market. What remains to be seen is how well these therapies will perform in conventional clinical practice and when, if ever, regeneration will become a major paradigm in medicine.
Nobel Prize Goes to Regenerative Medical Pioneers
On October 7th, two scientists who have made major contributions to the advancement of regenerative medicine were awarded the Nobel Prize in Physiology or Medicine. John B. Gurdon of the University of Cambridge in England was honored for his work on cloning in the early 1960s and Shinya Yamanaka of Kyoto University in Japan was honored for his 2006 discovery of induced pluripotent stem cells (iPS cells). Dr. Yamanaka’s work in particular offers a compelling work-around for some of the sticky cell sourcing issues (e.g., ethics associated with use of embryonic stem cells) that have plagued the cell therapy industry and thus hindered commercialization efforts. Check out this brief, informative interview with Dr. Yamanaka.