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Muscle engraftment of myogenic progenitor cells following intraarterial transplantation

Cell‐based therapy continues to be a promising avenue for the treatment of Duchenne muscular dystrophy (DMD), an X‐linked skeletal muscle–wasting disease. Recently, we demonstrated that freshly isolated myogenic progenitors contained within the adult skeletal muscle side population (SP) can engraft into dystrophic fibers of nonirradiated mdx5cv mice after intravenous transplantation. Engraftment rates, however, have not been therapeutically significant, achieving at most 1% of skeletal muscle myofibers expressing protein from donor‐derived nuclei. To enhance the engraftment of transplanted myogenic progenitors, an intraarterial delivery method was adapted from a previously described procedure. Cultured, lentivirus‐transduced skeletal muscle SP cells, derived from mdx5cv mice, were transplanted into the femoral artery of noninjured mdx5cv mice. Based on the expression of microdystrophin or green fluorescent protein (GFP) transgenes in host muscle, sections of the recipient muscles exhibited 5%–8% of skeletal muscle fibers expressing donor‐derived transgenes. Further, donor muscle SP cells, which did not express any myogenic markers prior to transplant, expressed the satellite cell transcription factor, Pax7, and the muscle‐specific intermediate filament, desmin, after extravasation into host muscle. The expression of these muscle‐specific markers indicates that progenitors within the side population can differentiate along the myogenic lineage after intraarterial transplantation and extravasation into host muscle. Given that femoral artery catheterization is a common, safe clinical procedure and that the transplantation of cultured adult muscle progenitor cells has proven to be safe in mice, our data may represent a step toward the improvement of cell‐based therapies for DMD and other myogenic disorders. Muscle Nerve, 2006