Tim Stüdemann1, Judith Rössinger2,1, Christoph Manthey2,1, Birgit Geertz2, Rajiven Srikantharajah2,1, Constantin von Bibra2,1, Aya Shibamiya2,1, Maria Köhne2,3,1, Antonius Wiehler4, J Simon Wiegert5, Thomas Eschenhagen2,1, Florian Weinberger2,1. 1. German Centre for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lubeck, Germany (T.S., J.R., C.M., R.S., C.v.B., A.S., M.K., T.E., F.W.). 2. Department of Experimental Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Germany (T.S., J.R., C.M., B.G., R.S., C.v.B., A.S., M.K., T.E., F.W.). 3. Surgery for Congenital Heart Disease, University Heart & Vascular Center Hamburg, Germany (M.K.). 4. Department of Psychiatry, Service Hospitalo-Universitaire, Groupe Hospitalier Universitaire Paris Psychiatrie & Neurosciences, Universite de Paris, France (A.W.). 5. Research Group Synaptic Wiring and Information Processing, Centre for Molecular Neurobiology Hamburg, Germany (J.S.W.).
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.
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.
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