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

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AI Med cover, Vol. 1, No. 2 (2025)
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Submitted: 2025-04-04
Accepted: 2025-06-19
Published: 2025-06-30
DOI: https://doi.org/10.71423/aimed.20250630
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

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Liu Hanxiang
School of Medical Imaging, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou 221004, China
Yijia Li
Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Huixian Zhou
Department of Internal Medicine, Montefiore Medical Center Wakefield Campus, 600 East 233rd Street, Bronx, NY 10466, USA
Yixin Yang
Department of Clinical Medicine, The First Clinical Medical College, Norman Bethune University of Medical Sciences, Jilin 130021, China
Rongkai Yan
Department of Radiology, Ohio State University, Columbus, OH 43210, USA
Xiaofeng Zhang
Greenwich Hospital, Yale New Haven Health, Greenwich, CT 06519, USA
Yutong Miao
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, China
Siyuan Song
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
Lingyu Bao
Department of Internal Medicine, Montefiore Medical Center Wakefield Campus, 600 East 233rd Street, Bronx, NY 10466, USA

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.
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Article Details

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Vol. 1 No. 2 (2025)

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Computer Science and Artificial Intelligence
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This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

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). https://doi.org/10.71423/aimed.20250630

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