title: Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro.
abstract: It has long been held as scientific fact that soon after birth, cardiomyocytes cease dividing, thus explaining the limited restoration of cardiac function after a heart attack. Recent demonstrations of cardiac myocyte differentiation observed in vitro or after in vivo transplantation of adult stem cells from blood, fat, skeletal muscle, or heart have challenged this view. Analysis of these studies has been complicated by the large disparity in the magnitude of effects seen by different groups and obscured by the recently appreciated process of in vivo stem-cell fusion. We now show a novel population of nonsatellite cells in adult murine skeletal muscle that progress under standard primary cell-culture conditions to autonomously beating cardiomyocytes. Their differentiation into beating cardiomyocytes is characterized here by video microscopy, confocal-detected calcium transients, electron microscopy, immunofluorescent cardiac-specific markers, and single-cell patch recordings of cardiac action potentials. Within 2 d after tail-vein injection of these marked cells into a mouse model of acute infarction, the marked cells are visible in the heart. By 6 d they begin to differentiate without fusing to recipient cardiac cells. Three months later, the tagged cells are visible as striated heart muscle restricted to the region of the cardiac infarct.
authors.affiliation: Molecular Physiology Section, Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
authors.forename: Steve O
authors.initials: SO
authors.lastname: Winitsky
authors.forename: Thiru V
authors.initials: TV
authors.lastname: Gopal
authors.forename: Shahin
authors.initials: S
authors.lastname: Hassanzadeh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Divina
authors.initials: D
authors.lastname: Gryder
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rogawski
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeda
authors.forename: Zu X
authors.initials: ZX
authors.lastname: Yu
authors.forename: Yu H
authors.initials: YH
authors.lastname: Xu
authors.forename: Neal D
authors.initials: ND
authors.lastname: Epstein
mesh_terms: D000200:Action Potentials; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D032342:Muscle Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques