title: Cardiac Regeneration: Lessons From Development.
abstract: Palliative surgery for congenital heart disease has allowed patients with previously lethal heart malformations to survive and, in most cases, to thrive. However, these procedures often place pressure and volume loads on the heart, and over time, these chronic loads can cause heart failure. Current therapeutic options for initial surgery and chronic heart failure that results from failed palliation are limited, in part, by the mammalian heart's low inherent capacity to form new cardiomyocytes. Surmounting the heart regeneration barrier would transform the treatment of congenital, as well as acquired, heart disease and likewise would enable development of personalized, in vitro cardiac disease models. Although these remain distant goals, studies of heart development are illuminating the path forward and suggest unique opportunities for heart regeneration, particularly in fetal and neonatal periods. Here, we review major lessons from heart development that inform current and future studies directed at enhancing cardiac regeneration.
authors.affiliation: From the Cardiovascular Institute, School of Medicine, Stanford University, CA (F.X.G., S.L.P., S.M.W.); Department of Cardiology, Boston Children's Hospital, MA (Y.G., N.J.V., W.T.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.L.P.), Division of Cardiovascular Medicine, Department of Medicine (S.M.W.), and Institute of Stem Cell and Regenerative Biology, School of Medicine, Stanford, CA (F.X.G., S.L.P., S.M.W.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (W.T.P.).
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Galdos
authors.affiliation: From the Cardiovascular Institute, School of Medicine, Stanford University, CA (F.X.G., S.L.P., S.M.W.); Department of Cardiology, Boston Children's Hospital, MA (Y.G., N.J.V., W.T.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.L.P.), Division of Cardiovascular Medicine, Department of Medicine (S.M.W.), and Institute of Stem Cell and Regenerative Biology, School of Medicine, Stanford, CA (F.X.G., S.L.P., S.M.W.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (W.T.P.).
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: From the Cardiovascular Institute, School of Medicine, Stanford University, CA (F.X.G., S.L.P., S.M.W.); Department of Cardiology, Boston Children's Hospital, MA (Y.G., N.J.V., W.T.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.L.P.), Division of Cardiovascular Medicine, Department of Medicine (S.M.W.), and Institute of Stem Cell and Regenerative Biology, School of Medicine, Stanford, CA (F.X.G., S.L.P., S.M.W.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (W.T.P.).
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Paige
authors.affiliation: From the Cardiovascular Institute, School of Medicine, Stanford University, CA (F.X.G., S.L.P., S.M.W.); Department of Cardiology, Boston Children's Hospital, MA (Y.G., N.J.V., W.T.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.L.P.), Division of Cardiovascular Medicine, Department of Medicine (S.M.W.), and Institute of Stem Cell and Regenerative Biology, School of Medicine, Stanford, CA (F.X.G., S.L.P., S.M.W.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (W.T.P.).
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: VanDusen
authors.affiliation: From the Cardiovascular Institute, School of Medicine, Stanford University, CA (F.X.G., S.L.P., S.M.W.); Department of Cardiology, Boston Children's Hospital, MA (Y.G., N.J.V., W.T.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.L.P.), Division of Cardiovascular Medicine, Department of Medicine (S.M.W.), and Institute of Stem Cell and Regenerative Biology, School of Medicine, Stanford, CA (F.X.G., S.L.P., S.M.W.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (W.T.P.). smwu@stanford.edu wpu@pulab.org.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wu
authors.affiliation: From the Cardiovascular Institute, School of Medicine, Stanford University, CA (F.X.G., S.L.P., S.M.W.); Department of Cardiology, Boston Children's Hospital, MA (Y.G., N.J.V., W.T.P.); Division of Pediatric Cardiology, Department of Pediatrics (S.L.P.), Division of Cardiovascular Medicine, Department of Medicine (S.M.W.), and Institute of Stem Cell and Regenerative Biology, School of Medicine, Stanford, CA (F.X.G., S.L.P., S.M.W.); and Harvard Stem Cell Institute, Harvard University, Cambridge, MA (W.T.P.). smwu@stanford.edu wpu@pulab.org.
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
mesh_terms: D000818:Animals; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006331:Heart Diseases / Q000628:therapy*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods*; D015398:Signal Transduction
keywords: cardiac development; cardiac regeneration; cardiomyocyte maturation; signaling pathways; transcriptional regulation