HIF‑1&alpha; overexpression improves the efficacy of human induced pluripotent stem cell‑derived cardiomyocytes for cardiac repair following myocardial infarction

Du,Jianfeng; Wang,Tianbao; Xu,Liqing

doi:10.3892/mmr.2024.13405

HIF‑1α overexpression improves the efficacy of human induced pluripotent stem cell‑derived cardiomyocytes for cardiac repair following myocardial infarction

Authors:
- Jianfeng Du
- Tianbao Wang
- Liqing Xu
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Affiliations: Department of Cardiology, The Fourth People's Hospital of Shenyang, Shenyang, Liaoning 110000, P.R. China, Department of Cardiology, The Fourth People's Hospital of Shenyang, Shenyang, Liaoning 110000, P.R. China
Published online on: November 27, 2024 https://doi.org/10.3892/mmr.2024.13405
Article Number: 40
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial infarction (MI) is the leading cause of death worldwide and currently there are limited therapies that can regenerate the lost cardiac cells following MI. To enhance the therapeutic effects of human induced pluripotent stem cell‑derived cardiomyocytes (hiPSC‑CM) transplantation for treatment of MI, the present study sought to increase the pro‑angiogenic effect of hiPSC‑CM by overexpressing a mutated hypoxia‑inducible factor 1‑alpha (HIF‑1α; P402A; P564A) via lentivirus transfection. Morphology and the electrophysiology of the genetically engineered cell were both unchanged. The present study demonstrated that the proangiogenic factors in the conditioned medium of the HIF‑1α‑overexpressing hiPSC‑CM (HIF‑CM) were upregulated and subsequently resulted to the rescue of the tube forming ability and migratory ability of the hypoxia‑injured human umbilical vein endothelial cells. Using a MI mouse model, the present study demonstrated that the transplantation of HIF‑CM greatly improved cardiac function, decreased scar size, promoted the concentration of the proangiogenic factors in circulation and promoted the neovessel formation in mice with MI. In conclusion, HIF‑1α‑overexpressing hiPSC‑CM could increase the angiogenesis of endothelial cells and mediate cardioprotection in mouse following MI.

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