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

Zhongyan Chen; Xiujian Yu; Minxia Ke; Hao Li; Yun Jiang; Peng Zhang; Jiliang Tan; Nan Cao; Huang-Tian Yang

doi:10.1016/j.yjmcc.2024.10.002

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

J Mol Cell Cardiol. 2024 Oct 9:S0022-2828(24)00163-9. doi: 10.1016/j.yjmcc.2024.10.002. Online ahead of print.

Authors

Zhongyan Chen¹, Xiujian Yu², Minxia Ke², Hao Li², Yun Jiang³, Peng Zhang³, Jiliang Tan², Nan Cao⁴, Huang-Tian Yang⁵

Affiliations

¹ 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.
² 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.
³ 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; Translational Medical Center for Stem Cell Therapy & Institutes of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, PR China.
⁴ Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong 510080, PR China.
⁵ 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; Translational Medical Center for Stem Cell Therapy & Institutes of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, PR China. Electronic address: htyang@sinh.ac.cn.

PMID: 39393445
DOI: 10.1016/j.yjmcc.2024.10.002

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.

Keywords: Cardiomyocyte dedifferentiation; Cardiomyocyte proliferation; Cardiovascular progenitor cells; Myocardial infarction; PI3K/Akt pathway.