Determination of the effective dose of bone marrow mononuclear cell therapy for bone healing in vivo

INTRODUCTION: Cell-based therapy by bone marrow mononuclear cells (BMC) in a large-sized bone defect has already shown improved vascularization and new bone formation. First clinical trials are already being conducted. BMC were isolated from bone marrow aspirate and given back to patients in combination with a scaffold within some hours. However, the optimal concentration of BMC has not yet been determined for bone healing. With this study, we want to determine the optimal dosage of the BMC in the bone defect to support bone healing. MATERIAL AND METHODS: Scaffolds with increasing BMC concentrations were inserted into a 5 mm femoral defect, cell concentrations of 2 × 10(6) BMC/mL, 1 × 10(7) BMC/mL and 2 × 10(7) BMC/mL were used. Based on the initial cell number used to colonize the scaffolds, the groups are designated 1 × 10(6), 5 × 10(6) and 1 × 10(7) group. Bone healing was assessed biomechanically, radiologically (µCT), and histologically after 8 weeks healing time. RESULTS: Improved bone healing parameters were noted in the 1 × 10(6) and 5 × 10(6) BMC groups. A significantly higher BMD was observed in the 1 × 10(6) BMC group compared to the other groups. Histologically, a significantly increased bone growth in the defect area was observed in group 5 × 10(6) BMC. This finding could be supported radiologically. CONCLUSION: It was shown that the effective dose of BMC for bone defect healing ranges from 2 × 10(6) BMC/mL to 1 × 10(7) BMC/mL. This concentration range seems to be the therapeutic window for BMC-supported therapy of large bone defects. However, further studies are necessary to clarify the exact BMC-dose dependent mechanisms of bone defect healing and to determine the therapeutically effective range more precisely.