Dystrophin expression in muscle after injection of donor myogenic cells

Skuk D et al. (2006) Dystrophin expression in muscles of Duchenne muscular dystrophy patients after high-density injections of normal myogenic cells. J Neuropathol Exp Neurol 65: 371–386

Researchers in Canada have evaluated the effect of the implantation of donor muscle precursor cells (MPCs) on the expression of dystrophin in patients with Duchenne muscular dystrophy. In nine patients, cultured MPCs from a parent were injected at 1–2 mm intervals into a 0.25 cm³ or 1 cm³ section of a tibialis anterior muscle. Control injections of saline were administered to the contralateral muscle of each patient.

Muscle biopsies taken 4 weeks after MPC implantation revealed expression of donor dystrophin in eight patients, with the percentage of myofibers expressing dystrophin varying from 3.5% to 26%. In addition to hybrid myofibers resulting from fusion of MPCs with existing fibers, small sections of entirely dystrophin-positive fibers, resulting from fusion of implanted MPCs with one another, were detected.

Previous attempts to induce dystrophin expression by MPC implantation in patients with muscular dystrophy have produced disappointing results. The authors state that a high density of injections is necessary for successful implantation, as MPCs do not diffuse from the injection site but fuse with fibers reached by the injection; fusion with fibers might also be assisted by damage caused by the injections. Previous studies used immunosuppressive agents such as ciclosporin or cyclophosphamide, which can damage implanted cells; the present study used tacrolimus, which seemed effective in preventing graft rejection in most cases, although substantial lymphocyte infiltration of the graft site was observed in two patients. Monitoring the immune response by comparison of graft and control sites is important, say the authors.