Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD.
Muscle disorders such as Duchenne muscular dystrophy (DMD) still need effective treatments, and mesenchymal stem cells (MSCs) may constitute an attractive cell therapy alternative because they are multipotent and accessible in adult tissues. We have previously shown that human multipotent adipose-derived stem (hMADS) cells were able to restore dystrophin expression in the mdx mouse. The goal of this work was to improve the myogenic potential of hMADS cells and assess the impact on muscle repair. Forced expression of MyoD in vitro strongly induced myogenic differentiation while the adipogenic differentiation was inhibited. Moreover, MyoD-expressing hMADS cells had the capacity to fuse with DMD myoblasts and to restore dystrophin expression. Importantly, transplantation of these modified hMADS cells into injured muscles of immunodepressed Rag2(-/-)gammaC(-/-) mice resulted in a substantial increase in the number of hMADS cell-derived fibers. Our approach combined the easy access of MSCs from adipose tissue, the highly efficient lentiviral transduction of these cells, and the specific improvement of myogenic differentiation through the forced expression of MyoD. Altogether our results highlight the capacity of modified hMADS cells to contribute to muscle repair and their potential to deliver a repairing gene to dystrophic muscles.
Institute of Developmental Biology and Cancer, University of Nice Sophia-Antipolis, CNRS, UMR6543, Nice, France.
Sébastien
S
Goudenege
Didier F
DF
Pisani
Brigitte
B
Wdziekonski
James P
JP
Di Santo
Claude
C
Bagnis
Christian
C
Dani
Claude A
CA
Dechesne
D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D002478:Cells, Cultured; D016189:Dystrophin / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016189:Dystrophin; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein