Breakthroughs in Cell Therapy for Heart Disease: Focus on Cardiosphere-Derived Cells

Mayo Foundation for Medical Education and Research



Mayo Clin Proc. 2014;89(6):850-858

Eduardo Marbán, MD, PhD



The clinical reality of cell therapy for heart disease dates back to the 1990s, when autologous skeletal myoblasts were first transplanted into failing hearts during open-chest surgery. Since then, the focus has shifted to bone marrowederived cells and, more recently, cells extracted from the heart itself. Although progress has been nonlinear and often disheartening, the field has nevertheless made remarkable progress. Six major breakthroughs are notable: (1) the establishment of safety with intracoronary delivery; (2) thefinding that therapeutic regeneration is possible; (3) the increase in allogeneic cell therapy; (4) the effect of increasing mechanistic insights; (5) glimmers of clinical efficacy; and (6) the progression to phase 2 and 3 studies. This article individually reviews these landmark developments in detail and concludes that thefield has reached a new phase of maturity where the prospect of clinical impact is increasingly imminent.



In the past several years, we have progressed from a profusion of hype to the point of having a solid basis for moving forward. With the good fortune of prevalent safety to date, we have managed to avoid the sort of debacle that derailed gene therapy for more than a decade. The evidence that therapeutic regeneration is possible, in a setting where conventional wisdom teaches that scar is irreversible, catapults the field onto a new plane yet to be achieved by any other treatment approach. The increasing evidence that allogeneic cells can be safe and effective takes cell preparation and manufacturing into the commercial mainstream and away from the cottage industry paradigm where it has been stalled for so long. Our increasing insights into the mechanism of action of transplanted cells helps us to decide what is and is not rational as we set priorities for future work. The glimmers of clinical efficacy in trials to date, coupled with the increasing number of advanced-phase clinical studies currently in progress, give new reasons for excitement. Other laudable developments not reviewed here include efforts to increase efficacy by conditioning the myocardial environment (eg, CELLWAVE trial54) or enhancing cardiogenesis of nonresident stem cells (eg, Cardiopoietic Stem Cell Therapy in Heart Failure trial55); such efforts can only enhance progress. In summary, the field has reached an unprecedented phase of maturity in which the prospect of clinical effect is increasingly plausible, if not likely. Exciting times lie ahead.


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