Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.
Stem Cell Res Ther
; 15(1): 73, 2024 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-38475911
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Pluripotentes Induzidas
/
Insuficiência Cardíaca
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cell Res Ther
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão