Mesenchymal and myogenic precursor cells : old partners for few interactions

In adult tissues, somatic stem cells represent a cell reservoir involved in physiological or pathological cell replacement. In several myopathies, chronic inflammation causes fibrotic infiltrations and adipose deposition within degenerating tissue. Starting from this evidence, we developed an experimental model for mimicking in vitro the effects of a damaged muscle on a specific stem cell population; the method is based on the simultaneous culture of stem cells and muscle tissue sections, in a microenvironment divided by a porous membrane, that guarantees soluble factors exchange but not cell migration. Human blood and adipose derived stem cells were grown in presence of normal (C57BL mouse) or dystrophic (mdx mouse model) muscle sections. Blood derived stem cells, co-cultured with muscle sections, showed an increase in cell proliferation and expression of mesenchymal markers, such as CD105, CD44, CD90, CD73 and CD29; moreover, they were able to express early myogenic differentiation markers, such as Myf5. Instead, human adipose derived stem cells showed an opposite behaviour; cells cultured in presence of both normal and dystrophic muscle tissue sections displayed an adipogenic differentiation. Moreover, the number of cells derived from the adipose mesenchymal stem cells and expressing Oil Red O lipid vacuole, Perilipin A and FABP4 was higher in the presence of dystrophic than normal muscle sections. These data suggest that the factors released by degenerating dystrophic muscle tissue may determine the commitment of mesenchymal stem cells into an adipogenic lineage underlying a new paradigm of the role of mesenchymal stem cells in the adipose formation of dystrophic muscle tissue