人胚胎干细胞衍生的心血管祖细胞通过激活 PI3K/Akt 通路刺激心肌细胞周期活动。

Human embryonic stem cell-derived cardiovascular progenitor cells stimulate cardiomyocyte cell cycle activity via activating the PI3K/Akt pathway.

机构信息

CAS Key Laboratory of Tissue Microenvironment and Tumor, Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences (CAS), CAS, Shanghai 200031, PR China; Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong 510080, PR China.

出版信息

J Mol Cell Cardiol. 2024 Dec;197:5-10. doi: 10.1016/j.yjmcc.2024.10.002. Epub 2024 Oct 10.

DOI:10.1016/j.yjmcc.2024.10.002

PMID:39393445

Abstract

Promoting endogenous cardiomyocyte proliferation is crucial for repairing infarcted hearts. Implantation of human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) promotes healing of infarcted hearts. However, little is known regarding their impact on host cardiomyocyte proliferation. Here, we revealed that hCVPC implantation into mouse infarcted hearts induced dedifferentiation and cell cycle re-entry of host cardiomyocytes, which was further confirmed in vitro by hCVPC-conditioned medium. Mechanistically, the PI3K/Akt signaling pathway mediated hCVPC-induced cardiomyocyte cell cycle re-entry. The findings reveal the novel function of hCVPCs in triggering cardiomyocyte dedifferentiation and cell cycle activation and highlight a strategy utilizing cells at early developmental stages to rejuvenate adult cardiomyocytes.

摘要

促进内源性心肌细胞增殖对于修复梗死心脏至关重要。植入人多能干细胞衍生的心血管祖细胞（hCVPC）可促进梗死心脏的愈合。然而，关于它们对宿主心肌细胞增殖的影响知之甚少。在这里，我们揭示了 hCVPC 植入到小鼠梗死心脏中诱导了宿主心肌细胞的去分化和细胞周期再进入，这在 hCVPC 条件培养基体外进一步得到了证实。在机制上，PI3K/Akt 信号通路介导了 hCVPC 诱导的心肌细胞细胞周期再进入。这些发现揭示了 hCVPC 在触发心肌细胞去分化和细胞周期激活方面的新功能，并强调了利用早期发育阶段的细胞来恢复成年心肌细胞活力的策略。