THE NEW STRATEGY FOR FRACTURE HEALING BY EX-VIVO EXPANDED BONE MARROW CD34 POSITIVE PROGENITOR CELLS

Introduction Failures in fracture healing are mainly caused by a lack of neovascularization. We have previously demonstrated that G-CSF-mobilized peripheral blood (GM-PB) CD34+ cells, an endothelial progenitor enriched cell population, contributed to fracture healing via vasculogenesis and osteogenesis. We postulated the hypothesis that local transplantation of culture expanded bone marrow (cEx-BM) CD34+ cells could exhibit therapeutic potential for fracture healing. Materials BM CD34+ cells were cultured in specific medium with 5 growth factors for 1week. A reproducible model of femoral fracture was created in nude rats with periosteum cauterization, which leads to nonunion at 8 weeks post-fracture. Rats received local administration of the following cells or PBS alone(1)cEx-BM, (2)BM, (3)GM-PB CD34+ cells or (4)PBS. Results Our 7-day culture expansion technique allowed us to obtain 23 times of BM CD34+ cells maintaining 60% purity of CD34 positivity. cEx-BM CD34+ cells exhibited striking therapeutic efficacy for unhealing fracture promoting neovascularization and osteogenesis in sites of fracture. Moreover, cEx-BM CD34+ cells showed high capacity of colony formation and osteogenic differentiation. Conclusion BM CD34+ cells can be obtained from the fracture site at the time of primary operation and stored for further use, autologous culture expanded BM CD34+ cell transplantation therapy would be not only a simple but also powerful therapeutic strategy for unhealing fracture.