Abstract
Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.
Highlights
Human induced pluripotent stem cells were developed by Dr Shinya Yamanaka more than 10 years ago [1]. This technology allows pluripotent stem cells to be derived from healthy persons, as well as patients. human induced pluripotent stem cell (hiPSC) have been used in multiple fields, leading to significant technological and therapeutic developments. hiPSC-derived cardiomyocytes (CMs) have been used to model several major cardiomyopathies, including ion related, structural, and metabolic cardiomyopathy, providing new insights into the mechanism underlying the disease phenotype
We provide an overview of hiPSC-CMs and their features, including characterization, maturation, and tissue engineering
After transplantation into healthy neonatal rat hearts, hiPSC-CMs exhibited an adult-like phenotype in structure, function, and gene expression profile within 2 months, indicating that the maturation is accelerated in a noncell-autonomous manner [161]. hiPSC-CMs can achieve further maturation in a fast way even when transplanted into a diseased heart. hiPSC-CMs derived from an Arrhythmogenic cardiomyopathy (ACM) patient were transplanted into neonatal animals and expressed more mature morphology after 1 month, including T-tubule formation, Cx43 expression, and calcium dynamics [162]
Summary
Human induced pluripotent stem cells (hiPSCs) were developed by Dr Shinya Yamanaka more than 10 years ago [1] This technology allows pluripotent stem cells to be derived from healthy persons, as well as patients. A potential genetic therapy based on CRISPR/Cas and adeno-associated virus has been proposed and validated in an hiPSC disease model Another promising application of hiPSC-CMs is drug toxicity screening (Figure 1); despite the remaining issues such as immaturity and heterogeneity within the hiPSC-derived CM culture, a new paradigm based on hiPSC-CMs has been proposed for more accurate prediction of the proarrhythmia risk. We provide an overview of hiPSC-CMs and their features, including characterization, maturation, and tissue engineering Their applications in cardiac disease modeling and new drug testing paradigms are summarized and discussed
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