title: Differential regenerative capacity of neonatal mouse hearts after cryoinjury.
abstract: Neonatal mouse hearts fully regenerate after ventricular resection similar to adult zebrafish. We established cryoinjury models to determine if different types and varying degrees of severity in cardiac injuries trigger different responses in neonatal mouse hearts. In contrast to ventricular resection, neonatal mouse hearts fail to regenerate and show severe impairment of cardiac function post transmural cryoinjury. However, neonatal hearts fully recover after non-transmural cryoinjury. Interestingly, cardiomyocyte proliferation does not significantly increase in neonatal mouse hearts after cryoinjuries. Epicardial activation and new coronary vessel formation occur after cryoinjury. The profibrotic marker PAI-1 is highly expressed after transmural but not non-transmural cryoinjuries, which may contribute to the differential scarring. Our results suggest that regenerative medicine strategies for heart injuries should vary depending on the nature of the injury.
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: Ali
authors.initials: A
authors.lastname: Darehzereshki
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: Nicole
authors.initials: N
authors.lastname: Rubin
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gamba
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: James
authors.initials: J
authors.lastname: Fraser
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California.
authors.forename: Joshua
authors.initials: J
authors.lastname: Billings
authors.affiliation: Broad Center of Stem Cell and Regenerative Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Robabeh
authors.initials: R
authors.lastname: Mohammadzadeh
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: John
authors.initials: J
authors.lastname: Wood
authors.affiliation: The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: David
authors.initials: D
authors.lastname: Warburton
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kaartinen
authors.affiliation: Heart Institute, Los Angeles, California; The Saban Research Institute of Children׳s Hospital Los Angeles, Los Angeles, California; Department of Surgery, Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address: clien@chla.usc.edu.
authors.forename: Ching-Ling
authors.initials: CL
authors.lastname: Lien
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D001808:Blood Vessels / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D004452:Echocardiography; D005615:Freezing; D006321:Heart / Q000502:physiology*; D006335:Heart Injuries / Q000503:physiopathology*; D006352:Heart Ventricles / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D012038:Regeneration; D013997:Time Factors
chemical_list: D053148:Caspase 3
keywords: Cardiomyocyte proliferation; Cryoinjury; Epicardium; Neonatal mouse heart regeneration; Neovascularization