Human Synovial Membrane-Derived Mesenchymal Stem Cells For Skeletal Muscle Repair.

Cosimo De Bari, Francesco Dell'Accio, Johan Neys, Frank P Luyten Leuven, Belgium

OBJECTIVE:   Spontaneous repair of skeletal muscle is normally mediated by the satellite cells that surround muscle fibers. In muscle disorders, in which this process does not occur effectively, the availability of a sufficient amount of functional satellite cells may be limiting. Alternative sources of myogenic progenitor cells are therefore desirable.

We have identified and characterized multipotent mesenchymal stem cells (MSCs) from adult human synovial membrane (SM) (De Bari et al, Arthritis and Rheumatism 2001, in press). In the present work, we assessed the capability of these MSCs to contribute to skeletal muscle repair in vivo.

METHODS:   Cell populations were enzymatically released from the SM of knee joints of adult human donors, and expanded in monolayer with serial passages at confluence. At different passages, SM-derived MSCs were injected into chemically injured tibialis anterior muscle of nude mice.

Time-point analysis was performed by semiquantitative RT-PCR using primers specific for the human genes. The identification of human cells was done by in situ hybridization for human-specific alu repeats and cell tracking using labeling techniques.

RESULTS:   Human SM-derived MSCs were capable of contributing to the repair of a chemically injured skeletal muscle into a nude mouse model. Gene expression analysis at different time-points revealed that differentiation into the skeletal muscle phenotype is associated with a molecular cascade that culminates with the long-term expression of dystrophin and myosin heavy chain. We also show that the in vivo myogenic potential of these cells is independent of donor age and is conserved after storage in liquid nitrogen.

CONCLUSION:   Human SM-derived MSCs are easily accessible, expandable, and transducable. Importantly, the preservation of their biological characteristics after storage in liquid nitrogen guarantees a versatile availability of autologous progenitor cells. SM-derived MSCs are therefore candidates for cell-based therapeutic approaches for postnatal skeletal muscle engineering and repair.