title: A systematic analysis of neonatal mouse heart regeneration after apical resection.
abstract: The finding that neonatal mice are able to regenerate myocardium after apical resection has recently been questioned. We determined if heart regeneration is influenced by the size of cardiac resection and whether surgical retraction of the ventricular apex results in an increase in cardiomyocyte cell cycle activity. We performed moderate or large apical ventricular resections on neonatal mice and quantified scar infiltration into the left ventricular wall at 21 days post-surgery. Moderately resected hearts had 15±2% of the wall infiltrated by a collagen scar; significantly greater scar infiltration (23±4%) was observed in hearts with large resections. Resected hearts had higher levels of cardiomyocyte cell cycle activity relative to sham hearts. Surgically retracting the ventricle often resulted in fibrosis and induced cardiomyocyte cell cycle activity that were comparable to that of resected hearts. We conclude that apical resection in neonatal mice induces cardiomyocyte cell cycle activity and neomyogenesis, although scarring can occur. Surgical technique and definition of approach to assessing the extent of regeneration are both critical when using the neonatal mouse apical resection model.
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Donald Marion
authors.initials: DM
authors.lastname: Bryant
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Caitlin Claire
authors.initials: CC
authors.lastname: O'Meara
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nhi Ngoc
authors.initials: NN
authors.lastname: Ho
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gannon
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, The Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02139, USA. Electronic address: RLee@Partners.org.
authors.forename: Richard Theodore
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006348:Cardiac Surgical Procedures; D002453:Cell Cycle; D005355:Fibrosis; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000601:surgery; D051379:Mice; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D012038:Regeneration / Q000502:physiology*
keywords: Apical resection; Cardiac regeneration; Fibrosis; Neomyogenesis