A Clinical Trial of Induced Pluripotent Stem Cells for Heart Disease Begins Next Year

Induced pluripotent stem cells (iPSCs) were from the very first seen as a promising biotechnology. The approach to reprogramming cells from a patient sample into iPSCs costs little and is easy for any life science lab to work with. This offers the potential to generate patient matched cells of any type in a reliable manner, which in turn enables development of a range of potential regenerative therapies. As is always the case, moving from the lab to the clinic has progressed at a very slow pace, however. The regulatory system demands absolute certainty and enormous expense, and the primary result is that it takes a very long time to make any sort of progress towards commercial application of technologies proven in the laboratory. Further, and as is the case here, these incentives direct researchers away from using patient-matched cells in favor of standard donor sources even when that causes worse outcomes for patients. The gap between what is possible and what is permitted increases with every passing year. At some point, and in some way, this must end.

Early next year, a small clinical trial will begin in Japan, marking the first time reprogrammed stem cells will be deployed to help regenerate injured hearts. A team will implant sheets - each consisting of 100 million stem-cell derived cardiomyocytes - onto the hearts of three patients with advanced heart failure. The cardiac study is only the second-ever clinical application of induced pluripotent stem (iPS) cells, the first being an iPS-cell transplant to treat macular degeneration of the eye, which also took place in Japan. While it is a big deal to pioneer such a technology clinically, the trial also has its risks, unknowns, and critics.

Japan's health ministry conditionally approved the heart experiment in May, with the goal of assessing the safety of the procedure. If the first trial and a later one enrolling 10 patients prove successful, the treatment will be made commercially available soon under a new fast-track system in Japan designed to speed up the development of regenerative therapies. Since the trial was announced, several Japanese researchers have voiced their concerns. One of them notes that the trail participants will receive iPS-derived cells from a donor, instead of from their own tissue, and will have to be placed on immunosuppressants for three months to prevent rejection. The researchers running the trials say that creating cardiomyocytes derived from a patient's own cells is not always an option, because the reprogramming process takes a long time. Providing off-the-shelf treatments is a more feasible route to address heart failure. "Cell therapy using a patient's own cells seems to be not suitable for industrialization."

While preclinical work with iPS cells has proven effective in improving heart function in mice, pig, and monkey models, it's not quite clear by which mechanism the cells are promoting muscle regeneration. It's still unknown whether these cells actually integrate into the heart and become beating heart cells, or whether they just release factors and help existing heart cells. Research in pigs suggests that iPS cell-derived cardiomyocytes promote regeneration of the heart by secreting certain cytokines that stimulate the native heart muscle to grow.