title: Quality metrics for stem cell-derived cardiac myocytes.
abstract: Advances in stem cell manufacturing methods have made it possible to produce stem cell-derived cardiac myocytes at industrial scales for in vitro muscle physiology research purposes. Although FDA-mandated quality assurance metrics address safety issues in the manufacture of stem cell-based products, no standardized guidelines currently exist for the evaluation of stem cell-derived myocyte functionality. As a result, it is unclear whether the various stem cell-derived myocyte cell lines on the market perform similarly, or whether any of them accurately recapitulate the characteristics of native cardiac myocytes. We propose a multiparametric quality assessment rubric in which genetic, structural, electrophysiological, and contractile measurements are coupled with comparison against values for these measurements that are representative of the ventricular myocyte phenotype. We demonstrated this procedure using commercially available, mass-produced murine embryonic stem cell- and induced pluripotent stem cell-derived myocytes compared with a neonatal mouse ventricular myocyte target phenotype in coupled in vitro assays.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sheehy
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasqualini
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Grosberg
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Aratyn-Schaus
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016000:Cluster Analysis; D055724:Electrophysiological Phenomena; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix; D020869:Gene Expression Profiling; D048091:Guided Tissue Regeneration; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000378:metabolism; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism