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Review
. 2019 Sep 6;20(18):4381.
doi: 10.3390/ijms20184381.

Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies

Andreas Brodehl  1 , Hans Ebbinghaus  2 , Marcus-André Deutsch  3 , Jan Gummert  4   5 , Anna Gärtner  6 , Sandra Ratnavadivel  7 , Hendrik Milting  8
Affiliations
Review

Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies

Andreas Brodehl et al. Int J Mol Sci. .

Abstract

In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.

Keywords: ARVC; DCM; HCM; LVNC; NCCM; RCM; cardiomyocytes; cardiomyopathies; cardiovascular genetics; induced pluripotent stem cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic overview on cardiomyopathy associated genes and related clinical phenotypes. DCM—Dilated cardiomyopathy. HCM—Hypertrophic cardiomyopathy, ACM—Arrhythmogenic cardiomyopathy, NCCM—Non-compaction cardiomyopathy, RCM—Restrictive cardiomyopathy (Images of the DCM or HCM heart were licensed from shutterstock.com).
Figure 2
Figure 2
Schematic overview about different delivery methods of the Yamanaka factors into somatic primary cells for reprogramming (sub-figures for the cell types and viruses were licensed from shutterstock.com).
See this image and copyright information in PMC

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