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.