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Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy

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Human iPSC-derived Disease Models for Drug Discovery

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 281))

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Abstract

Drug attrition rates have increased over the past few years, accompanied with growing costs for the pharmaceutical industry and consumers. Lack of in vitro models connecting the results of toxicity screening assays with clinical outcomes accounts for this high attrition rate. The emergence of cardiomyocytes derived from human pluripotent stem cells provides an amenable source of cells for disease modeling, drug discovery, and cardiotoxicity screening. Functionally similar to to embryonic stem cells, but with fewer ethical concerns, induced pluripotent stem cells (iPSCs) can recapitulate patient-specific genetic backgrounds, which would be a huge revolution for personalized medicine. The generated iPSC-derived cardiomyocytes (iPSC-CMs) represent different subtypes including ventricular-, atrial-, and nodal-like cardiomyocytes. Purifying these subtypes for chamber-specific drug screening presents opportunities and challenges. In this chapter, we discuss the strategies for the purification of iPSC-CMs, the use of iPSC-CMs for drug discovery and cardiotoxicity test, and the current limitations of iPSC-CMs that should be overcome for wider and more precise cardiovascular applications.

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Authors and Affiliations

  1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Ziwei Pan & Ping Liang

  2. Institute of Translational Medicine, Zhejiang University, Hangzhou, China

    Ziwei Pan & Ping Liang

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  1. Ziwei Pan
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  2. Ping Liang
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Correspondence to Ping Liang .

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Editors and Affiliations

  1. Center for Prevention and Treatment of Visual Loss; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA

    Markus H. Kuehn

  2. School of Pharmacy, Qingdao University, Qingdao, Shandong, China

    Wei Zhu

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Pan, Z., Liang, P. (2023). Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy. In: Kuehn, M.H., Zhu, W. (eds) Human iPSC-derived Disease Models for Drug Discovery. Handbook of Experimental Pharmacology, vol 281. Springer, Cham. https://doi.org/10.1007/164_2023_663

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