title: Modelling sarcomeric cardiomyopathies in the dish: from human heart samples to iPSC cardiomyocytes.
abstract: One of the obstacles to a better understanding of the pathogenesis of human cardiomyopathies has been poor availability of heart-tissue samples at early stages of disease development. This has possibly changed by the advent of patient-derived induced pluripotent stem cell (hiPSC) from which cardiomyocytes can be derived in vitro. The main promise of hiPSC technology is that by capturing the effects of thousands of individual gene variants, the phenotype of differentiated derivatives of these cells will provide more information on a particular disease than simple genotyping. This article summarizes what is known about the 'human cardiomyopathy or heart failure phenotype in vitro', which constitutes the reference for modelling sarcomeric cardiomyopathies in hiPSC-derived cardiomyocytes. The current techniques for hiPSC generation and cardiac myocyte differentiation are briefly reviewed and the few published reports of hiPSC models of sarcomeric cardiomyopathies described. A discussion of promises and challenges of hiPSC-modelling of sarcomeric cardiomyopathies and individualized approaches is followed by a number of questions that, in the view of the authors, need to be answered before the true potential of this technology can be evaluated.
authors.affiliation: Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg Eppendorf, Martinistr. 52, 20246 Hamburg, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck t.eschenhagen@uke.de bjorn.knollmann@vanderbilt.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Centre, Einthovenweg 20, 2333ZC Leiden, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Mummery
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, 2215 Garland Ave, Nashville, TN 37232, USA t.eschenhagen@uke.de bjorn.knollmann@vanderbilt.edu.
authors.forename: Bjorn C
authors.initials: BC
authors.lastname: Knollmann
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D002454:Cell Differentiation; D002478:Cells, Cultured; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D008955:Models, Cardiovascular; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology*; D057170:Translational Research, Biomedical / Q000379:methods*
chemical_list: D005819:Genetic Markers
keywords: Disease modeling; Disease phenotype; Heart Failure; Induced pluripotent stem cells; Sarcomeric cardiomyopathy