title: Human pluripotent stem cells: Prospects and challenges as a source of cardiomyocytes for in vitro modeling and cell-based cardiac repair.
abstract: Human pluripotent stem cells (PSCs) represent an attractive source of cardiomyocytes with potential applications including disease modeling, drug discovery and safety screening, and novel cell-based cardiac therapies. Insights from embryology have contributed to the development of efficient, reliable methods capable of generating large quantities of human PSC-cardiomyocytes with cardiac purities ranging up to 90%. However, for human PSCs to meet their full potential, the field must identify methods to generate cardiomyocyte populations that are uniform in subtype (e.g. homogeneous ventricular cardiomyocytes) and have more mature structural and functional properties. For in vivo applications, cardiomyocyte production must be highly scalable and clinical grade, and we will need to overcome challenges including graft cell death, immune rejection, arrhythmogenesis, and tumorigenic potential. Here we discuss the types of human PSCs, commonly used methods to guide their differentiation into cardiomyocytes, the phenotype of the resultant cardiomyocytes, and the remaining obstacles to their successful translation.
authors.affiliation: Division of Cardiology, Department of Medicine, USA; Department of Genome Sciences, USA; Institute for Stem Cell and Regenerative Medicine, USA; Center for Cardiovascular Biology, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hartman
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, USA; Center for Cardiovascular Biology, USA; Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Dao-Fu
authors.initials: DF
authors.lastname: Dai
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, USA; Center for Cardiovascular Biology, USA; Department of Pathology, University of Washington, Seattle, WA, USA. Electronic address: laflamme@u.washington.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Laflamme
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology; D004707:Endoderm / Q000166:cytology; D006331:Heart Diseases / Q000628:therapy*; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D023822:Tissue Engineering
keywords: Cardiac regeneration; Cardiac repair; Cardiovascular disease; Disease modeling; Drug discovery; Embryonic stem cells; Heart failure; Induced pluripotent stem cells