Zhang Zhiwei, Li Xiaoting, Zhuang Jiawei, Ding Qingwei, Zheng Hui, Ma Teng, Meng Qingyou, Gao Ling
Department of Vascular Surgery, General Surgery Clinical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
JACC Basic Transl Sci. 2024 Feb 7;9(5):557-573. doi: 10.1016/j.jacbts.2023.11.005. eCollection 2024 May.
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.
近期证据表明,低植入率限制了人诱导多能干细胞衍生心肌细胞(hiPSC-CMs)在心肌梗死后心脏修复中的疗效。在本研究中,我们试图通过增强移植的hiPSC-CMs的增殖能力来克服这一限制。我们发现,miR-590-3p过表达增加了hiPSC-CMs的增殖能力。miR-590-3p过表达增加了植入细胞的数量,并且在心肌修复方面比对照细胞具有更高的疗效。此外,我们证实了在猪心脏中使用miR-590-3p过表达的hiPSC-CMs的安全性。这些结果表明,miR-590-3p过表达刺激hiPSC-CM细胞周期重新进入以诱导细胞增殖,并提高了心肌梗死的治疗效果。