Survival of bone marrow-derived mesenchymal stem cells in a xenotransplantation model.

Mesenchymal stem cells (MSCs) are immunoprivileged and the allogeneic MSCs implantation has been used to facilitate tissue repairs such as bone and cartilage defect. The present study aimed to investigate the feasibility of xenogeneic MSCs implantation. Green fluorescent protein (GFP) transgenic rat bone marrow-derived MSCs were loaded into HA/TCP Skelite blocks and implanted intramuscularly into the quadriceps of the MF1 and SCID mice. After 11 weeks, the implants were harvested and processed for further examinations. The peripheral blood mononuclear cells of each animal were also collected to measure the in vitro immune responses using mixed lymphocyte culture and cytotoxic assay. In the MF1 mice, some surviving MSCs were found in the explants after 11 weeks of implantation, but there was no sign of new bone formation as neither osteocalcin mRNA nor osteoid tissues were detected in the explants; the lymphocyte proliferation and cytotoxicity against donor MSCs were significantly increased in the animals with the xenogeneic MSCs implantation compared with the control littermates without transplantation. In the control SCID mice, osteoid tissues derived from the implanted MSCs were found in the explants; no difference of lymphocyte proliferation and cytotoxicity against the donor MSCs was detected between the SCID mice with or without MSCs implantation. The data suggested that rat MSCs survived the 11 weeks of xenotransplantation in the MF1 mice, but the increased host immune sensitization led to the impaired in vivo osteogenesis potential of MSCs.