Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury

Circulation. 2022 Oct 11;146(15):1159-1169. doi: 10.1161/CIRCULATIONAHA.122.060124. Epub 2022 Sep 8.

Abstract

Background: Transplantation of pluripotent stem cell-derived cardiomyocytes represents a promising therapeutic strategy for cardiac regeneration, and the first clinical studies in patients with heart failure have commenced. Yet, little is known about the mechanism of action underlying graft-induced benefits. Here, we explored whether transplanted cardiomyocytes actively contribute to heart function.

Methods: We injected cardiomyocytes with an optogenetic off-on switch in a guinea pig cardiac injury model.

Results: Light-induced inhibition of engrafted cardiomyocyte contractility resulted in a rapid decrease of left ventricular function in ≈50% (7/13) animals that was fully reversible with the offset of photostimulation.

Conclusions: Our optogenetic approach demonstrates that transplanted cardiomyocytes can actively participate in heart function, supporting the hypothesis that the delivery of new force-generating myocardium can serve as a regenerative therapeutic strategy.

Keywords: cell transplantation; regenerative medicine; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Guinea Pigs
  • Myocardium
  • Myocytes, Cardiac* / transplantation
  • Pluripotent Stem Cells* / physiology
  • Ventricular Function, Left