Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro

Steve O. Winitsky, Thiru V. Gopal, Shahin Hassanzadeh, Hiroshi Takahashi, Divina Gryder, Michael A Rogawski, Kazuyo Takeda, Zu X. Yu, Yu H. Xu, Neal D. Epstein

Research output: Contribution to journalArticle

85 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)662-671
Number of pages10
JournalPLoS Biology
Volume3
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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    Winitsky, S. O., Gopal, T. V., Hassanzadeh, S., Takahashi, H., Gryder, D., Rogawski, M. A., Takeda, K., Yu, Z. X., Xu, Y. H., & Epstein, N. D. (2005). Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro. PLoS Biology, 3(4), 662-671. https://doi.org/10.1371/journal.pbio.0030087