Human multipotent adipose-derived stem cells restore dystrophin expression of Duchenne skeletal-muscle cells in vitro.
BACKGROUND
DMD (Duchenne muscular dystrophy) is a devastating X-linked disorder characterized by progressive muscle degeneration and weakness. The use of cell therapy for the repair of defective muscle is being pursued as a possible treatment for DMD. Mesenchymal stem cells have the potential to differentiate and display a myogenic phenotype in vitro. Since liposuctioned human fat is available in large quantities, it may be an ideal source of stem cells for therapeutic applications. ASCs (adipose-derived stem cells) are able to restore dystrophin expression in the muscles of mdx (X-linked muscular dystrophy) mice. However, the outcome when these cells interact with human dystrophic muscle is still unknown.


RESULTS
We show here that ASCs participate in myotube formation when cultured together with differentiating human DMD myoblasts, resulting in the restoration of dystrophin expression. Similarly, dystrophin was induced when ASCs were co-cultivated with DMD myotubes. Experiments with GFP (green fluorescent protein)-positive ASCs and DAPI (4',6-diamidino-2-phenylindole)-stained DMD myoblasts indicated that ASCs participate in human myogenesis through cellular fusion.


CONCLUSIONS
These results show that ASCs have the potential to interact with dystrophic muscle cells, restoring dystrophin expression of DMD cells in vitro. The possibility of using adipose tissue as a source of stem cell therapies for muscular diseases is extremely exciting.
Vieira
Natássia M
NM
Human Genome Research Center, Biosciences Institute, University of São Paulo, Rua do Matão, CEP 05508-090, n.106 Cidade Universitária, São Paulo, SP, Brazil.
Brandalise
Vanessa
V
Zucconi
Eder
E
Jazedje
Tatiana
T
Secco
Mariane
M
Nunes
Viviane A
VA
Strauss
Bryan E
BE
Vainzof
Mariz
M
Zatz
Mayana
M
D000273:Adipose Tissue / Q000166:cytology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002469:Cell Separation; D018920:Coculture Techniques; D016189:Dystrophin / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology*; D032342:Muscle Cells / Q000166:cytology*; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D014161:Transduction, Genetic
D016189:Dystrophin