Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury
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Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury. / 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.
in: CIRCULATION, Jahrgang 146, Nr. 15, 11.10.2022, S. 1159-1169.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury
AU - Stüdemann, Tim
AU - Rössinger, Judith
AU - Manthey, Christoph
AU - Geertz, Birgit
AU - Srikantharajah, Rajiven
AU - von Bibra, Constantin
AU - Shibamiya, Aya
AU - Köhne, Maria
AU - Wiehler, Antonius
AU - Wiegert, J Simon
AU - Eschenhagen, Thomas
AU - Weinberger, Florian
PY - 2022/10/11
Y1 - 2022/10/11
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Differentiation/physiology
KW - Guinea Pigs
KW - Myocardium
KW - Myocytes, Cardiac/transplantation
KW - Pluripotent Stem Cells/physiology
KW - Ventricular Function, Left
U2 - 10.1161/CIRCULATIONAHA.122.060124
DO - 10.1161/CIRCULATIONAHA.122.060124
M3 - SCORING: Journal article
C2 - 36073365
VL - 146
SP - 1159
EP - 1169
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 15
ER -