Ex vivo generation of mature and functional human smooth muscle cells differentiated from skeletal myoblasts

• Published in: Experimental cell research 2007-04, Vol.313 (7), p.1337-1346
• Main Authors: Le Ricousse-Roussanne, Sophie, Larghero, Jerome, Zini, Jean-Marc, Barateau, Veronique, Foubert, Philippe, Uzan, Georges, Liu, Xuhui, Lacassagne, Marie-Noelle, Ternaux, Brigitte, Robert, Isabelle, Benbunan, Marc, Vilquin, Jean-Thomas, Vauchez, Karine, Tobelem, Gerard, Marolleau, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - analysis; Cell Differentiation; Cell therapy; Cells, Cultured; Cellular Biology; Collagen - pharmacology; Differentiation; Drug Combinations; Epithelial Cells - physiology; Female; Functionality; Gene expression; Humans; Laminin - pharmacology; Life Sciences; Mice; Mice, Inbred NOD; Mice, SCID; Muscle Fibers, Skeletal - physiology; Muscular system; Myoblasts; Myoblasts, Skeletal - drug effects; Myoblasts, Skeletal - metabolism; Myoblasts, Skeletal - physiology; Myoblasts, Skeletal - transplantation; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - physiology; Myocytes, Smooth Muscle - transplantation; Neovascularization, Physiologic; Proteoglycans - pharmacology; Smooth muscle cell; Tissue Culture Techniques; Transplantation, Heterologous; Vascular Endothelial Growth Factor A - pharmacology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2007.01.022

We described the ex vivo production of mature and functional human smooth muscle cells (SMCs) derived from skeletal myoblasts. Initially, myoblasts expressed all myogenic cell-related markers such as Myf5, MyoD and Myogenin and differentiate into myotubes. After culture in a medium containing vascular endothelial growth factor (VEGF), these cells were shown to have adopted a differentiated SMC identity as demonstrated by αSMA, SM22α, calponin and smooth muscle-myosin heavy chain expression. Moreover, the cells cultured in the presence of VEGF did not express MyoD anymore and were unable to fuse in multinucleated myotubes. We demonstrated that myoblasts-derived SMCs (MDSMCs) interacted with endothelial cells to form, in vitro, a capillary-like network in three-dimensional collagen culture and, in vivo, a functional vascular structure in a Matrigel implant in nonobese diabetic-severe combined immunodeficient mice. Based on the easily available tissue source and their differentiation into functional SMCs, these data argue that skeletal myoblasts might represent an important tool for SMCs-based cell therapy.