Author:

Keywords:

Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Lineage, Cells, Cultured, Disease Models, Animal, Female, Humans, Mesoderm, Mice, Mice, Inbred mdx, Mice, Knockout, Mice, Nude, Middle Aged, Muscle Fibers, Muscle, Skeletal, Muscular Dystrophy, Animal, Research Support, Non-U.S. Gov't, Satellite Cells, Skeletal Muscle, Stem Cell Transplantation, Stem Cells, Synovial Membrane, Science & Technology, Life Sciences & Biomedicine, Cell Biology, Duchenne muscular dystrophy, dystrophin, cell transplantation, muscle development, insulin-like growth factor I, SATELLITE CELLS, BONE-MARROW, TEMPORAL EXPRESSION, MUSCULAR-DYSTROPHY, MYOGENIN GENE, MDX MOUSE, NAKED DNA, IN-VIVO, MICE, MYOBLASTS, Muscle Fibers, Skeletal, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

Abstract:

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.