1. Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury.
- Author
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Stüdemann T, Rössinger J, Manthey C, Geertz B, Srikantharajah R, von Bibra C, Shibamiya A, Köhne M, Wiehler A, Wiegert JS, Eschenhagen T, and Weinberger F
- Subjects
- Animals, Cell Differentiation physiology, Guinea Pigs, Myocardium, Ventricular Function, Left, Myocytes, Cardiac transplantation, Pluripotent Stem Cells physiology
- 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.
- Published
- 2022
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