Abstract: Transplantation of pluripotent stem cell-derived cardiomyocytes represents an innovative therapeutic strategy for heart failure. Studies in small and large animals have demonstrated functional recovery of left ventricular function after cardiomyocyte transplantation1–4, and first clinical studies are currently underway5. Yet, the mechanism of action underlying graft-induced benefit is unknown6. Here we demonstrate that transplanted cardiomyocytes actively contribute to heart function. We transplanted cardiomyocytes with an optogenetic off-on switch in a guinea pig cardiac injury model. Light-induced inhibition of engrafted cardiomyocyte contractility resulted in a rapid decrease of left ventricular function that was fully reversible with the offset of photostimulation. Hence, our optogenetic approach demonstrated that transplanted cardiomyocytes actively participate in heart function, supporting the hypothesis that the delivery of new force-generating myocardium can serve as a regenerative therapeutic strategy.

Journal Link: 10.1101/2021.11.23.469715 Journal Link: Publisher Website Journal Link: Downaload PDF Journal Link: Google Scholar