Human epicardium-derived cells fuse with high efficiency with skeletal myotubes and differentiate toward the skeletal muscle phenotype: A comparison study with stromal and endothelial cells

Antonietta Gentile, Gabriele Toietta, Vincenzo Pazzano, Vasileios D. Tsiopoulos, Ada Francesca Giglio, Filippo Crea, Giulio Pompilio, Maurizio C. Capogrossi, Giuliana Di Rocco

Research output: Contribution to journalArticle

Abstract

Recent studies have underscored a role for the epicardium as a source of multipotent cells. Here, we investigate the myogenic potential of adult human epicardium-derived cells (EPDCs) and analyze their ability to undergo skeletal myogenesis when cultured with differentiating primary myoblasts. Results are compared to those obtained with mesenchymal stromal cells (MSCs) and with endothelial cells, another mesodermal derivative. We demonstrate that EPDCs spontaneously fuse with pre-existing myotubes with an efficiency that is significantly higher than that of other cells. Although at a low frequency, endothelial cells may also contribute to myotube formation. In all cases analyzed, after entering the myotube, nonmuscle nuclei are reprogrammed to express muscle-specific genes. The fusion competence of nonmyogenic cells in vitro parallels their ability to reconstitute dystrophin expression in mdx mice. We additionally show that vascular cell adhesion molecule 1 (VCAM1) expression levels of nonmuscle cells are modulated by soluble factors secreted by skeletal myoblasts and that VCAM1 function is required for fusion to occur. Finally, treatment with interleukin (IL)-4 or IL-13, two cytokines released by differentiating myotubes, increases VCAM1 expression and enhances the rate of fusion of EPDCs and MSCs, but not that of endothelial cells.

Original languageEnglish
Pages (from-to)581-592
Number of pages12
JournalMolecular Biology of the Cell
Volume22
Issue number5
DOIs
Publication statusPublished - Mar 1 2011

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Pericardium
Skeletal Muscle Fibers
Stromal Cells
Skeletal Muscle
Endothelial Cells
Efficiency
Phenotype
Vascular Cell Adhesion Molecule-1
Aptitude
Mesenchymal Stromal Cells
Skeletal Myoblasts
Inbred mdx Mouse
Dystrophin
Interleukin-13
Muscle Development
Myoblasts
Interleukin-4
Mental Competency
Cytokines
Muscles

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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Human epicardium-derived cells fuse with high efficiency with skeletal myotubes and differentiate toward the skeletal muscle phenotype : A comparison study with stromal and endothelial cells. / Gentile, Antonietta; Toietta, Gabriele; Pazzano, Vincenzo; Tsiopoulos, Vasileios D.; Giglio, Ada Francesca; Crea, Filippo; Pompilio, Giulio; Capogrossi, Maurizio C.; Di Rocco, Giuliana.

In: Molecular Biology of the Cell, Vol. 22, No. 5, 01.03.2011, p. 581-592.

Research output: Contribution to journalArticle

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