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

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.

Scaffolds with increasing BMC concentrations were inserted into a 5 mm femoral defect, cell concentrations of 2 × 10⁶ BMC/mL, 1 × 10⁷ BMC/mL and 2 × 10⁷ BMC/mL were used. Based on the initial cell number used to colonize the scaffolds, the groups are designated 1 × 10⁶, 5 × 10⁶ and 1 × 10⁷ group. Bone healing was assessed biomechanically, radiologically (µCT), and histologically after 8 weeks healing time.

Improved bone healing parameters were noted in the 1 × 10⁶ and 5 × 10⁶ BMC groups. A significantly higher BMD was observed in the 1 × 10⁶ BMC group compared to the other groups. Histologically, a significantly increased bone growth in the defect area was observed in group 5 × 10⁶ BMC. This finding could be supported radiologically.

It was shown that the effective dose of BMC for bone defect healing ranges from 2 × 10⁶ BMC/mL to 1 × 10⁷ 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.