Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

Figure 10

 Autotransplantation of myoblasts genetically modified ex vivo in a nonhuman primate. Myoblasts were grown in vitro from a biopsy performed in a skeletal muscle of a cynomolgus monkey. The cells were infected in vitro with a lentivirus containing a cassette including a microdystrophin coupled to a V5 peptide tag. These myoblasts were intramuscularly injected in the same monkey, in the absence of immunosuppression, and the injected site was sampled 1 month later. The figure shows a transversal section of the biopsy of the cell-grafted region. The V5 fusion protein was detected by peroxidase immunodetection with an anti-V5 antibody counterstained with diluted hematoxylin. Myofibers expressing the V5-tagged micro-dystrophin are shown between arrowheads. The labeling is essentially sarcoplasmic, according to the normal location of dystrophin, although some intracellular pale staining is also observed. Some of the V5-positive myofibers exhibit internal nuclei, indicating recent regeneration. This is in agreement to the fact that the grafted cells participated in the regeneration of myofibers damaged by the injection needle. Without immunosuppression and in allogeneic conditions, these myofibers would be already rejected. In this case, not only the hybrid myofibers are still present after 1 month, but also there is no histological evidence of acute rejection (i.e., no lymphocyte accumulations around the hybrid myofibers). Scale bar = 100 μm.