Key Takeaways & Executive Findings
- •• Clinical-grade hiPSC-CM patches demonstrated safety with no tumorigenicity or genomic mutations in preclinical assessments. • hiPSC-CM patches improved cardiac function and promoted angiogenesis in a porcine myocardial infarction model. • No lethal arrhythmias were observed post-transplantation, supporting the safety profile of the patches. • The study provides proof-of-concept for the translational potential of hiPSC-CM patches in treating heart failure.
Abstract
Background Cell- or tissue-based regenerative therapy is an attractive approach to treat heart failure. A tissue patch that can safely and effectively repair damaged heart muscle would greatly improve outcomes for patients with heart failure. In this study, we conducted a preclinical proof-of-concept analysis of the efficacy and safety of clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches. Methods A clinical-grade hiPSC line was established using peripheral blood mononuclear cells from a healthy volunteer that was homozygous for human leukocyte antigens. The hiPSCs were differentiated into cardiomyocytes. The obtained hiPSC-CMs were cultured on temperature-responsive culture dishes for patch fabrication. The cellular characteristics, safety, and efficacy of hiPSCs, hiPSC-CMs, and hiPSC-CM patches were analyzed. Results The hiPSC-CMs expressed cardiomyocyte-specific genes and proteins, and electrophysiological analyses revealed that hiPSC-CMs exhibit similar properties to human primary myocardial cells. In vitro and in vivo safety studies indicated that tumorigenic cells were absent. Moreover, whole-genome and exome sequencing revealed no genomic mutations. General toxicity tests also showed no adverse events posttransplantation. A porcine model of myocardial infarction demonstrated significantly improved cardiac function and angiogenesis in response to cytokine secretion from hiPSC-CM patches. No lethal arrhythmias were observed. Conclusions hiPSC-CM patches are promising for future translational research and may have clinical application potential for the treatment of heart failure.
1. Introduction
Heart failure remains correlated with a high mortality rate despite advances in medical treatment. Novel treatment techniques are necessary to improve the outcomes of heart failure patients. Recent studies have illustrated that human induced pluripotent stem cells (hiPSCs) are a source of stem cells that can replace lost cells in diseased organs [1–3]. Moreover, hiPSC-derived cardiomyocytes (hiPSC-CMs), in the form of myocardial tissue patches, can be used to supply new cardiomyocytes to the heart, suggesting their potential clinical application in the treatment of heart failure [4–7].
However, there are major concerns regarding the safety and, particularly, the tumorigenicity of hiPSCs [8–10]. Adequate in vitro and in vivo preclinical studies on the safety and efficacy of hiPSC-CMs are necessary for the initiation of subsequent clinical trial investigations and the potential clinical application of this technique.
In this study, we determined whether a clinical-grade hiPSC-CM patch could serve as a functional myocardial tissue. We performed a preclinical study to ensure its safety and conducted a proof-of-concept analysis of hiPSC-CM patches in clinical applications.
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Shigeru Miyagawa, Takuji Kawamura, Emiko Ito, Maki Takeda, Hiroko Iseoka, Junya Yokoyama, Akima Harada, Noriko Mochizuki-Oda, Yukiko Imanishi-Ochi, Junjun Li, Masao Sasai, Fumiyo Kitaoka, Masaki Nomura, Naoki Amano, Tomoko Takahashi, Hiromi Dohi, Eiichi Morii, Yoshiki Sawa (2026). Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03690-8
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Frequently Asked Questions
What is the main purpose of this study?
The study aims to evaluate the efficacy and safety of clinical-grade human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches for the treatment of heart failure through preclinical proof-of-concept analysis.
How were the hiPSC-CM patches fabricated?
Clinical-grade hiPSCs were differentiated into cardiomyocytes, which were then cultured on temperature-responsive culture dishes to form patches.
What were the key safety findings?
The study found no tumorigenic cells, no genomic mutations, and no adverse events in general toxicity tests, indicating a favorable safety profile.
What were the efficacy results in the animal model?
In a porcine myocardial infarction model, hiPSC-CM patches significantly improved cardiac function and promoted angiogenesis, with no lethal arrhythmias observed.
What is the clinical significance of this research?
The results suggest that hiPSC-CM patches are promising for future translational research and may have clinical application potential for treating heart failure.
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