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HIF-1α 过表达提高了人诱导多能干细胞衍生的心肌细胞在心肌梗死后心脏修复中的疗效。

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

机构信息

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.

出版信息

Mol Med Rep. 2025 Feb;31(2). doi: 10.3892/mmr.2024.13405. Epub 2024 Nov 29.

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.

摘要

心肌梗死(MI)是全球范围内导致死亡的主要原因,目前仅有有限的疗法可以在 MI 后再生丢失的心肌细胞。为了增强人诱导多能干细胞衍生的心肌细胞(hiPSC-CM)移植治疗 MI 的治疗效果,本研究试图通过慢病毒转染过表达突变的缺氧诱导因子 1 ɑ(HIF-1ɑ;P402A;P564A)来增加 hiPSC-CM 的促血管生成作用。基因工程细胞的形态和电生理学均无变化。本研究表明,过表达 HIF-1ɑ 的 hiPSC-CM(HIF-CM)条件培养基中的促血管生成因子上调,随后挽救了缺氧损伤的人脐静脉内皮细胞的管形成能力和迁移能力。使用 MI 小鼠模型,本研究表明,HIF-CM 的移植极大地改善了心脏功能,减少了疤痕面积,促进了循环中促血管生成因子的浓度,并促进了 MI 小鼠的新血管形成。总之,过表达 HIF-1ɑ 的 hiPSC-CM 可增加内皮细胞的血管生成,并在 MI 后介导小鼠的心脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1cf/11626424/c9f2dac75f99/mmr-31-02-13405-g00.jpg

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