Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury. Issue 15 (8th September 2022)

• Record Type: Journal Article
• Authors: Stüdemann, Tim; Rössinger, Judith; Manthey, Christoph; Geertz, Birgit; Srikantharajah, Rajiven; von Bibra, Constantin; Shibamiya, Aya; Köhne, Maria; Wiehler, Antonius; Wiegert, J. Simon; Eschenhagen, Thomas; Weinberger, Florian
• Is Part Of: Circulation. Volume 146:Issue 15(2022)
• Page Start: 1159
• Page End: 1169
• Publication Date: 2022-09-08
• Subjects: cell transplantation -- regenerative medicine -- stem cells; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.122.060124
• Languages: English
• ISSNs: 0009-7322

Abstract

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.