Ex vivo generation of mature and functional human smooth muscle cells differentiated from skeletal myoblasts.
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 alphaSMA, SM22alpha, 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.
Le Ricousse-Roussanne
Sophie
S
Institut des Vaisseaux et du Sang et Centre de Recherche Cardiovasculaire, INSERM U689, Paris, France.
Larghero
Jerome
J
Zini
Jean-Marc
JM
Barateau
Veronique
V
Foubert
Philippe
P
Uzan
Georges
G
Liu
Xuhui
X
Lacassagne
Marie-Noelle
MN
Ternaux
Brigitte
B
Robert
Isabelle
I
Benbunan
Marc
M
Vilquin
Jean-Thomas
JT
Vauchez
Karine
K
Tobelem
Gerard
G
Marolleau
Jean-Pierre
JP
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D004338:Drug Combinations; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen