The Process of Engraftment of Myogenic Cells in Skeletal Muscles of Primates: Understanding Clinical Observations and Setting Directions in Cell Transplantation Research

We studied in macaques the evolution of the intramuscular transplantation of muscle precursor cells between the time of administration and the time at which the graft is considered stable. Satellite cell–derived myoblasts labeled with ß-galactosidase were transplanted into 1 cm(3) muscle regions following cell culture and transplantation protocols similar to our last clinical trials. These regions were biopsied 1 h, 1, 3, 7 d, and 3 wk later and analyzed by histology. We observed that the cell suspension leaks from the muscle bundles during injection toward the epimysium and perimysium, where most cells accumulate after transplantation. We observed evidence of necrosis, apoptosis, and mitosis in the accumulations of grafted cells, and of potential migration to participate in myofiber regeneration in the surrounding muscle bundles. After 3 wk, the compact accumulations of grafted cells left only some graft-derived myotubes and small myofibers in the perimysium. Hybrid myofibers were abundant in the muscle fascicles at 3 wk posttransplantation, and they most likely occur by grafted myoblasts that migrated from the peripheral accumulations than by the few remaining within the fascicles immediately after injection. These observations explain the findings in clinical trials of myoblast transplantation and provide information for the future research in cell therapy in myology.