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Article

Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression

Group of Molecular and Cellular Cardiology, Department of Circulation and Medical Imaging, Faculty of Medicine and Health, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(15), 8460; https://doi.org/10.3390/ijms25158460
Submission received: 13 June 2024 / Revised: 27 July 2024 / Accepted: 29 July 2024 / Published: 2 August 2024
(This article belongs to the Special Issue New Progress in Extracellular Vesicles)

Abstract

Experimental evidence, both in vitro and in vivo, has indicated cardioprotective effects of extracellular vesicles (EVs) derived from various cell types, including induced pluripotent stem cell-derived cardiomyocytes. The biological effects of EV secretion, particularly in the context of ischemia and cardiac electrophysiology, remain to be fully explored. Therefore, the goal of this study was to unveil the effects of exosome (EXO)-mediated cell–cell signaling during hypoxia by employing a simulated preconditioning approach on human-induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CMs). Electrophysiological activity of hIPSC-CMs was measured using a multielectrode array (MEA) system. A total of 16 h of hypoxic stress drastically increased the beat period. Moreover, hIPSC-CMs preconditioned with EXOs displayed significantly longer beat periods compared with non-treated cells after 16 h of hypoxia (+15.7%, p < 0.05). Furthermore, preconditioning with hypoxic EXOs resulted in faster excitation–contraction (EC) coupling compared with non-treated hIPSC-CMs after 16 h of hypoxia (−25.3%, p < 0.05). Additionally, microRNA (miR) sequencing and gene target prediction analysis of the non-treated and pre-conditioned hIPSC-CMs identified 10 differentially regulated miRs and 44 gene targets. These results shed light on the intricate involvement of miRs, emphasizing gene targets associated with cell survival, contraction, apoptosis, reactive oxygen species (ROS) regulation, and ion channel modulation. Overall, this study demonstrates that EXOs secreted by hIPSC-CM during hypoxia beneficially alter electrophysiological properties in recipient cells exposed to hypoxic stress, which could play a crucial role in the development of targeted interventions to improve outcomes in ischemic heart conditions.
Keywords: electrophysiology; excitation–contraction coupling; exosomes; hypoxia; next-generation sequencing; micro RNA modulation electrophysiology; excitation–contraction coupling; exosomes; hypoxia; next-generation sequencing; micro RNA modulation

Share and Cite

MDPI and ACS Style

Røsand, Ø.; Wang, J.; Scrimgeour, N.; Marwarha, G.; Høydal, M.A. Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression. Int. J. Mol. Sci. 2024, 25, 8460. https://doi.org/10.3390/ijms25158460

AMA Style

Røsand Ø, Wang J, Scrimgeour N, Marwarha G, Høydal MA. Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression. International Journal of Molecular Sciences. 2024; 25(15):8460. https://doi.org/10.3390/ijms25158460

Chicago/Turabian Style

Røsand, Øystein, Jianxiang Wang, Nathan Scrimgeour, Gurdeep Marwarha, and Morten Andre Høydal. 2024. "Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression" International Journal of Molecular Sciences 25, no. 15: 8460. https://doi.org/10.3390/ijms25158460

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