Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle inadult dystrophic mdx mice

It is commonly accepted, that regenerative capacity of striated muscle is c onfined to skeletal muscle by activation of satellite cells that normally r eside quiescent between the plasmalemma and the basement membrane of muscle fibers. Muscular dystrophies are characterized by repetitive cycles of de- and regeneration of skeletal muscle fibers and by the frequent involvement of the cardiac muscle. Since during the longstanding course of muscular dy strophies there is a permanent demand of myogenic progenitors we hypothesiz ed that this may necessitate a recruitment of additional myogenic precursor s from an undifferentiated, permanently renewed cell pool, such as bone mar row (BM) cells. To this end normal and dystrophic (mdx) female mice receive d bone marrow transplantation (BMT) from normal congenic male donor mice. A fter 70 days, histological sections of skeletal and cardiac muscle from BMT mice were probed for the donor-derived Y chromosomes. In normal BMT recipi ents, no Y chromosome-containing myonuclei were detected, either in skeleta l or in cardiac muscle. However, in all samples from dystrophic mdx skeleta l muscles Y chromosome-specific signals were detected within muscle fiber n uclei, which additionally were found to express the myoregulatory proteins myogenin and myf-5. Moreover, in the hearts of BMT-mdx mice single cardiomy ocytes with donor derived nuclei were identified, indicating, that even car diac muscle cells are able to regenerate by recruitment of circulating BM-d erived progenitors. Our findings suggest that further characterization and identification of the BM cells capable of undergoing myogenic differentiati on may have an outstanding impact on therapeutic strategies for diseases of skeletal and cardiac muscle.