miR-590-3p Overexpression Improves the Efficacy of hiPSC-CMs for Myocardial Repair

Zhiwei Zhang; Xiaoting Li; Jiawei Zhuang; Qingwei Ding; Hui Zheng; Teng Ma; Qingyou Meng; Ling Gao

doi:10.1016/j.jacbts.2023.11.005

miR-590-3p Overexpression Improves the Efficacy of hiPSC-CMs for Myocardial Repair

JACC Basic Transl Sci. 2024 Feb 7;9(5):557-573. doi: 10.1016/j.jacbts.2023.11.005. eCollection 2024 May.

Authors

Zhiwei Zhang¹, Xiaoting Li^{2

3}, Jiawei Zhuang⁴, Qingwei Ding¹, Hui Zheng¹, Teng Ma¹, Qingyou Meng¹, Ling Gao⁵

Affiliations

¹ Department of Vascular Surgery, General Surgery Clinical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Cardiology, Second Affiliated Hospital of Soochow University, Suzhou, China.
⁴ Department of Cardiovascular Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
⁵ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Recent evidence demonstrates that low engraftment rates limit the efficacy of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac repair after myocardial infarction. In this study, we attempted to overcome this limitation by enhancing the proliferative capacity of transplanted hiPSC-CMs. We found that miR-590-3p overexpression increased the proliferative capacity of hiPSC-CMs. miR-590-3p overexpression increased the number of engrafted cells and had a higher efficacy for myocardial repair than control cells. Moreover, we confirmed the safety of using miR-590-3p-overexpressing hiPSC-CMs in pig hearts. These results indicated that miR-590-3p overexpression stimulated hiPSC-CM cell cycle re-entry to induce cell proliferation and increased the therapeutic efficacy in MI.

Keywords: cell cycle; human induced pluripotent stem cells; miR-590-3p; myocardial infarction.