biostudies-literatureMiyagawa SJapan Agency of Medical Research and DevelopmentJapan Agency for Medical Research and Development73https://www.ebi.ac.uk/biostudies/studies/S-EPMC10935836biostudies-literatureUnknown15(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>hiPSC-CM patches are promising for future translational research and may have clinical application potential for the treatment of heart failure.Stem cell research & therapyPre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.PMC10935836JP17bk0104044JP20bm0204003Sawa YTakeda MDohi HLi JImanishi-Ochi YYokoyama JKawamura TKitaoka FNomura MIto ETakahashi TMorii ESasai MIseoka HHarada AMochizuki-Oda NAmano NMiyagawa SfalsePre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>hiPSC-CM patches are promising for future translational research and may have clinical application potential for the treatment of heart failure.2024-01-01T00:00:00Z2024 Mar2026-06-28T03:12:13.238Z2025-05-18T12:54:10.626ZS-EPMC109358363847591110.1186/s13287-024-03690-8