Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse.
Here, we report the isolation of a human multipotent adipose-derived stem (hMADS) cell population from adipose tissue of young donors. hMADS cells display normal karyotype; have active telomerase; proliferate >200 population doublings; and differentiate into adipocytes, osteoblasts, and myoblasts. Flow cytometry analysis indicates that hMADS cells are CD44+, CD49b+, CD105+, CD90+, CD13+, Stro-1(-), CD34-, CD15-, CD117-, Flk-1(-), gly-A(-), CD133-, HLA-DR(-), and HLA-I(low). Transplantation of hMADS cells into the mdx mouse, an animal model of Duchenne muscular dystrophy, results in substantial expression of human dystrophin in the injected tibialis anterior and the adjacent gastrocnemius muscle. Long-term engraftment of hMADS cells takes place in nonimmunocompromised animals. Based on the small amounts of an easily available tissue source, their strong capacity for expansion ex vivo, their multipotent differentiation, and their immune-privileged behavior, our results suggest that hMADS cells will be an important tool for muscle cell-mediated therapy.
Rodriguez
Anne-Marie
AM
Institut de Recherche Signalisation, Biologie du Développement et Cancer, UMR 6543 Centre National de la Recherche Scientifique, 06108 Nice Cedex 2, France.
Pisani
Didier
D
Dechesne
Claude A
CA
Turc-Carel
Claude
C
Kurzenne
Jean-Yves
JY
Wdziekonski
Brigitte
B
Villageois
Albert
A
Bagnis
Claude
C
Breittmayer
Jean-Philippe
JP
Groux
Hervé
H
Ailhaud
Gérard
G
Dani
Christian
C
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D016189:Dystrophin / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007121:Immunocompetence / Q000502:physiology*; D007150:Immunohistochemistry; D007223:Infant; D007621:Karyotyping; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D039902:Multipotent Stem Cells / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
D017931:DNA Primers; D016189:Dystrophin