Myoblast transplantation has long been studied as a potential therapy for Duchenne muscular dystrophy as the incorporation of donor myoblasts into host muscle allows the production of functional dystrophin protein. However, the clinical feasibility of this approach is limited by the poor survival of the donor cells in the weeks after transplantation. It has recently been determined that the intramuscular transplantation of large numbers of cells can lead to the formation of ischemic necrosis in the center of these cell masses. For this reason, the relationship between donor cell survival and the number of cells transplanted was investigated.Methods.
Myoblasts were prepared from the hind limb muscles of male C57BL/10Sn mice and transplanted into the tibialis anterior muscles of female mdx mice at one of the following amounts: 103, 104, 105, or 106 cells. The survival of the transplanted cells was analyzed using a Y chromosome-specific qPCR.Results.
It was found that donor cell survival was improved 1 week after transplantation when fewer myoblasts were transplanted, including the observation of donor cell proliferation after the transplantation of 103 myoblasts. However, concentration effects and long-term survival complicate the interpretation of these results.Conclusions.
These results indicate that early donor myoblast survival was dependent on the number of cells transplanted and the volume of liquid used to deliver them into the muscle. We believe that this finding has implications for the design and interpretation of future experimentation relating to intramuscular cell therapies.