Induced pluripotent stem cells in the inherited cardiomyopathies: From disease mechanisms to novel therapies.
Inherited cardiomyopathies lead to diverse clinical outcomes including heart failure, arrhythmias, and sudden death. Mutations in over 100 genes have been implicated in the pathogenesis of genetic heart diseases, including the main inherited cardiomyopathies, such as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies. Understanding how these gene mutations lead to clinical disease and the various secondary genetic and environmental factors, which may modify the clinical phenotype, are key areas of research ultimately influencing diagnosis and management of patients. The emergence of patient-derived induced pluripotent stem cells (iPSCs), which can be differentiated into functional cardiomyocytes (CMs) in vitro, may provide an exciting new approach to understand disease mechanisms underpinning inherited heart diseases. This review will focus specifically on the key role of iPSC-based studies in the inherited cardiomyopathies, both in their potential utility as well as the significant challenges they present.
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Newtown, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
Samantha Barratt
SB
Ross
Disciplines of Physiology, Anatomy & Histology, School of Medical Sciences, University of Sydney, Sydney, Australia.
Stuart T
ST
Fraser
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Newtown, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia. Electronic address: c.semsarian@centenary.org.au.
Christopher
C
Semsarian
D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D010641:Phenotype; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous
Cardiomyopathy; Genetic; Induced pluripotent stem cell; Inherited