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September 2022

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Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury

DZHK authors: Tim Stüdemann, Judith Rössinger, Christoph Manthey, Rajiven Srikantharajah, Constantin von Bibra, Aya Shibamiya, Maria Köhne, Thomas Eschenhagen, Florian Weinberger.

Circulation, 2022;146:1159–1169

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The adult heart has very limited regenerative capacity. Therefore, a heart infarction often leads to heart failure, a disease which currently has no curative therapy. The transplantation of stem cell-derived cardiomyocytes is a promising treatment opportunity which has been successful in preclinical models. Additionally, this approach has been translated into first clinical studies. However, the underlying mechanism of this therapy has not been elucidated. In this study we investigated if the transplanted cardiomyocytes actively participate in force generation of the left ventricle. Here we engineered stem cell-derived cardiomyocytes to switch off contractility using light. These cells have then been transplanted in a preclinical animal model. Switching off the cardiomyocytes in this model resulted in a reduction of cardiac function, an effect that was reversible upon the stop of photostimulation. These results show for the first time that transplanted cardiomyocytes are contributing actively to cardiac function and are therefore encouraging regarding ongoing and future clinical trials. Thus, the transplantation of stem cell derived cardiomyocytes might provide a conceptually new therapeutic strategy for heart failure patients.

Link to publication