دورية أكاديمية

Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.

التفاصيل البيبلوغرافية
العنوان: Pre-clinical evaluation of the efficacy and safety of human induced pluripotent stem cell-derived cardiomyocyte patch.
المؤلفون: Miyagawa, Shigeru, Kawamura, Takuji, Ito, Emiko, Takeda, Maki, Iseoka, Hiroko, Yokoyama, Junya, Harada, Akima, Mochizuki-Oda, Noriko, Imanishi-Ochi, Yukiko, Li, Junjun, Sasai, Masao, Kitaoka, Fumiyo, Nomura, Masaki, Amano, Naoki, Takahashi, Tomoko, Dohi, Hiromi, Morii, Eiichi, Sawa, Yoshiki
المصدر: Stem Cell Research & Therapy; 3/13/2024, Vol. 15 Issue 1, p1-15, 15p
مصطلحات موضوعية: MONONUCLEAR leukocytes, HLA histocompatibility antigens, WHOLE genome sequencing, HEART failure, MYOCARDIUM, TOXICITY testing, ARRHYTHMIA
مستخلص: 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. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:17576512
DOI:10.1186/s13287-024-03690-8