Study on molecular regulation of muscle regeneration by mesenchymal cells

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We found that CD31(-) CD45(-) side population (SP) cells in skeletal muscle are activated during muscle regeneration and promote the proliferation and the migration of grafted myoblasts. To further clarify the roles for CD31(-) CD45(-) SP cells, we generated CD248-sDTR-EGFP transgenic mice. However, the mice did not express sDTR-EGFP. This could be because the 1.0 kb upstream sequences of the CD248 gene were not enough to drive the expression of the reporter gene. We next analyzed the genome-wide gene expression pattern of mesenchymal cells (a descendent of CD31(-) CD45(-) SP cells) from dystrophin-deficient mice of different age. We found that mesenchymal cells in mdx mice experience cell senescence and immune response- and defense-related genes. These findings suggest that impaired muscle regeneration seen in advanced dystrophic muscle can be partly explained by exhausted mesenchymal cells, which otherwise promote muscle regeneration.