Human PSC-derived cardiac cells and their products: therapies for cardiac repair.

Despite the dramatic improvements in the management of patients with chronic heart failure which have occurred over the last decades, some of them still exhaust conventional drug-based therapies without being eligible for more aggressive options like heart transplantation or implantation of a left ventricular assist device. Cell therapy has thus emerged as a possible means of filling this niche. Multiple cell types have now been tested both in the laboratory but also in the clinics and it is fair to acknowledge that none of the clinical trials have yet conclusively proven the efficacy of cell-based approaches. These clinical studies, however, have entailed the use of cells from various sources but of non-cardiac lineage origins. Although this might not be the main reason for their failures, the discovery of pluripotent stem cells capable of generating cardiomyocytes now raises the hope that such cardiac-committed cells could be therapeutically more effective. In this review, we will first describe where we currently are with regard to the clinical trials using PSC-differentiated cells and discuss the main issues which remain to be addressed. In parallel, because the capacity of cells to stably engraft in the recipient heart has increasingly been questioned, it has been hypothesized that a major mechanism of action could be the cell-triggered release of biomolecules that foster host-associated reparative pathways. Thus, in the second part of this review, we will discuss the rationale, clinically relevant advantages and pitfalls associated with the use of these PSC "products".