Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane.
We have demonstrated previously that adult human synovial membrane-derived mesenchymal stem cells (hSM-MSCs) have myogenic potential in vitro (De Bari, C., F. Dell'Accio, P. Tylzanowski, and F.P. Luyten. 2001. Arthritis Rheum. 44:1928-1942). In the present study, we have characterized their myogenic differentiation in a nude mouse model of skeletal muscle regeneration and provide proof of principle of their potential use for muscle repair in the mdx mouse model of Duchenne muscular dystrophy. When implanted into regenerating nude mouse muscle, hSM-MSCs contributed to myofibers and to long term persisting functional satellite cells. No nuclear fusion hybrids were observed between donor human cells and host mouse muscle cells. Myogenic differentiation proceeded through a molecular cascade resembling embryonic muscle development. Differentiation was sensitive to environmental cues, since hSM-MSCs injected into the bloodstream engrafted in several tissues, but acquired the muscle phenotype only within skeletal muscle. When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor.
De Bari
Cosimo
C
Laboratory for Skeletal Development and Joint Disorders, Dept. of Rheumatology, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
Dell'Accio
Francesco
F
Vandenabeele
Frank
F
Vermeesch
Joris R
JR
Raymackers
Jean-Marc
JM
Luyten
Frank P
FP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D008819:Mice, Nude; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*