AI Article Synopsis
- The study explores the use of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches as a regenerative therapy for heart failure, aiming to safely repair damaged heart tissue.
- Researchers created a clinical-grade hiPSC line and differentiated them into cardiomyocytes, assessing their safety and effectiveness through in vitro and in vivo testing, including a porcine heart model.
- Results showed that hiPSC-CMs exhibited properties similar to natural heart cells, with no signs of tumor formation or adverse effects, and significantly improved heart function and blood vessel growth, indicating their potential for treating heart failure.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935836 | PMC |
| http://dx.doi.org/10.1186/s13287-024-03690-8 | DOI Listing |
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