Abstract
Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.
Highlights
Cardiovascular disease (CVD) and heart failure (HF) still represent the major causes of mortality and morbidity in the Western world [1]
Starting from the growing understanding of heart development and from new insight in the epigenetic control of cardiac differentiation, we covered the progressions obtained in the cell culture approach and in the differentiation methods, the analysis of the secretoma of the Human-induced pluripotent stem cells (hiPSCs) differentiated cell, the new advances in hiPSC-derived bioengineered cardiac tissues, the exploitation of iPSCs-cardiac myocytes (CMs) for the in vitro modeling of cardiac diseases or for cardiac safety testing of drug and, the immunological concerns associated with their clinical application
embryoid body formation assay (EB) are round, multi-cellular, 3D aggregates formed by hiPSCs and are able to differentiate into cells of all three germ layers including beating cardiomyocytes with low efficiency in the presence of fetal bovine serum [58,59]
Summary
Cardiovascular disease (CVD) and heart failure (HF) still represent the major causes of mortality and morbidity in the Western world [1]. The pathological basis is mainly related to the very limited ability of the heart to withstand injury and aging, which is due to insufficient cardioprotection combined with almost the complete lack of myocardial renewal. In such scenarios, cardiac transplantation still represents the ultimate therapeutic option for HF, it is severely hindered by the short supply of available donor hearts. Starting from the growing understanding of heart development and from new insight in the epigenetic control of cardiac differentiation, we covered the progressions obtained in the cell culture approach and in the differentiation methods, the analysis of the secretoma of the hiPSCs differentiated cell, the new advances in hiPSC-derived bioengineered cardiac tissues, the exploitation of iPSCs-CMs for the in vitro modeling of cardiac diseases or for cardiac safety testing of drug and, the immunological concerns associated with their clinical application
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