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Open Access Review

Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies

by Liu Hanxiang 1,# ,  Yijia Li 2,# ,  Huixian Zhou 3,# ,  Yixin Yang 4 ,  Rongkai Yan 5 ,  Xiaofeng Zhang 6 ,  Yutong Miao 7,* ,  Siyuan Song 8,*  and  Lingyu Bao 3,*
1
School of Medical Imaging, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou 221004, China
2
Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
3
Department of Internal Medicine, Montefiore Medical Center Wakefield Campus, 600 East 233rd Street, Bronx, NY 10466, USA
4
Department of Clinical Medicine, The First Clinical Medical College, Norman Bethune University of Medical Sciences, Jilin 130021, China
5
Department of Radiology, Ohio State University, Columbus, OH 43210, USA
6
Greenwich Hospital, Yale New Haven Health, Greenwich, CT 06519, USA
7
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, China
8
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
#
Contributed equally
*
Author to whom correspondence should be addressed.
AI Med  2025 1(2):6; https://doi.org/10.71423/aimed.20250630
Received: 4 April 2025 / Accepted: 19 June 2025 / Published Online: 30 June 2025
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Abstract

Ischemic heart disease (IHD) remains a major cause of global morbidity and mortality, with limited regenerative capacity of the adult myocardium posing a persistent therapeutic challenge. Stem cell-based interventions have emerged as a promising approach, offering the potential to restore cardiac function through angiogenesis, anti-fibrotic modulation, and tissue integration. This review comprehensively examines the therapeutic potential of three major cell types—induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), mesenchymal stem cells (MSCs), and cardiac progenitor cells (CPCs)—in both preclinical and clinical settings. iPSC-CMs demonstrate direct cardiomyocyte replacement and promote neovascularization via the VEGF/PI3K/Akt pathway. MSCs act primarily through paracrine signaling, attenuating fibrosis and inflammation via TGF-β/Smad2/3 activation, while CPCs support myocardial survival and integration through Notch signaling. Clinical trials highlight moderate improvements in left ventricular function and quality of life, particularly with MSC and CPC therapies. However, challenges persist, including cell immaturity, immune rejection, limited engraftment, and inconsistent long-term efficacy. Future directions emphasize strategies to enhance cell maturation, reduce immunogenicity, and refine clinical trial design. Integration of bioengineering techniques, gene modification, and personalized therapeutic platforms may ultimately enable the safe and effective translation of stem cell therapies into routine care for patients with IHD.

Keywords: Ischemic heart disease; stem cell therapy; induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs); mesenchymal stem cells (MSCs); cardiac progenitor cells (CPCs); VEGF/PI3K/Akt pathway; TGF-β/Smad signaling; Notch pathway; cardiac regeneration; clinical translation;
Copyright: © 2025 by Hanxiang, Li, Zhou, Yang, Yan, Zhang, Miao, Song and Bao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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APA Style
Hanxiang, L., Li, Y., Zhou, H., Yang, Y., Yan, R., Zhang, X., Miao, Y., Song, S., & Bao, L. (2025). Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies. AI Med, 1(2), 6. doi:10.71423/aimed.20250630
ACS Style
Hanxiang, L.; Li, Y.; Zhou, H.; Yang, Y.; Yan, R.; Zhang, X.; Miao, Y.; Song, S.; Bao, L. Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies. AI Med, 2025, 1, 6. doi:10.71423/aimed.20250630
AMA Style
Hanxiang L, Li Y, Zhou H et al.. Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies. AI Med; 2025, 1(2):6. doi:10.71423/aimed.20250630
Chicago/Turabian Style
Hanxiang, Liu; Li, Yijia; Zhou, Huixian; Yang, Yixin; Yan, Rongkai; Zhang, Xiaofeng; Miao, Yutong, and et al. 2025. "Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies" AI Med 1, no.2:6. doi:10.71423/aimed.20250630

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APA Style
Hanxiang, L., Li, Y., Zhou, H., Yang, Y., Yan, R., Zhang, X., Miao, Y., Song, S., & Bao, L. (2025). Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies. AI Med, 1(2), 6. doi:10.71423/aimed.20250630
ACS Style
Hanxiang, L.; Li, Y.; Zhou, H.; Yang, Y.; Yan, R.; Zhang, X.; Miao, Y.; Song, S.; Bao, L. Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies. AI Med, 2025, 1, 6. doi:10.71423/aimed.20250630
AMA Style
Hanxiang L, Li Y, Zhou H et al.. Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies. AI Med; 2025, 1(2):6. doi:10.71423/aimed.20250630
Chicago/Turabian Style
Hanxiang, Liu; Li, Yijia; Zhou, Huixian; Yang, Yixin; Yan, Rongkai; Zhang, Xiaofeng; Miao, Yutong, and et al. 2025. "Stem Cell-Based Regenerative Therapies for Ischemic Heart Disease: Mechanisms, Clinical Evidence, and Translational Strategies" AI Med 1, no.2:6. doi:10.71423/aimed.20250630

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