Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2025; 17(3): 101454
Published online Mar 26, 2025. doi: 10.4252/wjsc.v17.i3.101454
MiR-21-5p-enriched exosomes from hiPSC-derived cardiomyocytes exhibit superior cardiac repair efficacy compared to hiPSC-derived exosomes in a murine MI model
Jing-Jun Jin, Rong-Hua Liu, Jin-Yan Chen, Kun Wang, Jun-Yong Han, Dao-Shun Nie, Yu-Qing Gong, Bin Lin, Guo-Xing Weng
Jing-Jun Jin, Rong-Hua Liu, Jin-Yan Chen, Kun Wang, Jun-Yong Han, Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, Fujian Province, China
Dao-Shun Nie, Yu-Qing Gong, Bin Lin, Guo-Xing Weng, Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, Fujian Province, China
Co-corresponding authors: Jing-Jun Jin and Guo-Xing Weng.
Author contributions: Jin JJ and Weng GX contributed to the conceptualization, writing-review, and editing of this manuscript, and they contributed equally to this article and as co-corresponding authors; Liu RH, Chen JY, Nie DS, Gong YQ, and Lin B participated in the methodology of this manuscript; Liu RH, Chen JY, Wang K, and Han JY took part in the formal analysis, investigation, and data curation; Jin JJ and Liu RH contributed to the writing-original draft preparation; All authors have read and agreed to the published version of the manuscript.
Supported by the Nonprofit Research Institutes Foundation of Fujian Province, China, No. 2021R1012005 and No. 2021R1012003.
Institutional animal care and use committee statement: This study was carried out in accordance with the principles of the Basel Declaration. The study was approved by the Ethics Committee of Fujian Academy of Medical Sciences (Approval No. DL2021-09).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing-Jun Jin, Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, No. 7 Wusi Road, Fuzhou 350001, Fujian Province, China. yolanda_jin19@hotmail.com
Received: September 15, 2024
Revised: October 15, 2024
Accepted: January 15, 2025
Published online: March 26, 2025
Processing time: 187 Days and 3.4 Hours
Abstract
BACKGROUND

Heart disease remains a leading cause of mortality worldwide, with existing treatments often failing to effectively restore damaged myocardium. Human-induced pluripotent stem cells (hiPSCs) and their derivatives offer promising therapeutic options; however, challenges such as low retention, engraftment issues, and tumorigenic risks hinder their clinical utility. Recent focus has shifted to exosomes (exos) - nanoscale vesicles that facilitate intercellular communication - as a safer and more versatile alternative. Understanding the specific mechanisms and comparative efficacy of exos from hiPSCs vs hiPSC-derived cardiomyocytes (hiPSC-CMs) is crucial for advancing cardiac repair therapies.

AIM

To evaluate and compare the therapeutic efficacy of exos secreted by hiPSCs and hiPSC-CMs in cardiac repair, and to elucidate the role of microRNA 21-5p (miR-21-5p) in the observed effects.

METHODS

We differentiated hiPSCs into CMs using small molecule methods and characterized the cells and their exos.

RESULTS

Our findings indicate that hiPSC-CMs and their exos enhanced cardiac function, reduced infarct size, and decreased myocardial fibrosis in a murine myocardial infarction model. Notably, hiPSC-CM exos outperformed hiPSC-CM cell therapy, showing improved ejection fraction and reduced apoptosis. We identified miR-21-5p, a microRNA in hiPSC-CM exos, as crucial for CM survival. Exos with miR-21-5p were absorbed by AC16 cells, suggesting a mechanism for their cytoprotective effects.

CONCLUSION

Overall, hiPSC-CM exos could serve as a potent therapeutic agent for myocardial repair, laying the groundwork for future research into exos as a treatment for ischemic heart disease.

Keywords: Human-induced pluripotent stem cells; Human-induced pluripotent stem cell-derived cardiomyocytes; Myocardial infarction; Exosomes; MicroRNA 21-5p; Apoptosis

Core Tip: This study explored human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and their exosomes (exos) for myocardial infarction (MI) repair. Despite issues with hiPSC-CMs, exos are promising due to low immunogenicity. By differentiating hiPSCs and characterizing, it was found that they improved cardiac function in a murine MI model. hiPSC-CMs exos are superior, with microRNA 21-5p being key. Thus, they may be a strong agent for myocardial repair and inspire further research on exo treatment for heart disease.