Progress in myoblast transplantation: A potential treatment of dystrophies

Myoblast transplantation (MT) consists of injecting normal or genetically m odified myogenic cells into muscles, where they are expected to fuse and fo rm mature fibers. As an experimental approach to treat severe genetic muscl e diseases, MT was tested in dystrophic patients at the beginning of the 19 90s. Although these early clinical trials were unsuccessful, MT has progres sed through the research on animal models. Many factors that may condition the success of MT were identified in the last years. The present review upd ates our knowledge on MT and describes the different problems that have lim ited its success. Factors that were first underestimated, like the specific immune response after MT, are presently well characterized. Destruction of the hybrid fibers by activated T-lymphocytes and production of antibodies against the transplanted myoblasts take place after MT and are responsible for the graft rejection. The choice of the immunosuppression seems to be ve ry important, and FK506 is the best agent known to allow the best results a fter MT. Under FK506 immunosuppression, very efficient MT were obtained bot h in mice and monkeys. Moreover, in dystrophic mice it was demonstrated tha t MT ameliorates some phenotypical characteristics of the disease. The impr ovement of the survival of the transplanted cells and the increase of their migration into the injected tissue are presently under investigation. Some of the present research is directed also to bypass the immunosuppression b y using the patient's own cells for MT. In this sense, efforts are conducte d to introduce the normal gene into the patient's myoblasts before MT and t o improve the ability of these cells to proliferate in vitro. Micros. (C) 2 000 Wiley-Liss, Inc.