Bone regeneration using uncultured cells of bone marrow aspirate concentrate

Purpose: Regenerative therapy with cultured bone marrow MSCs is associated with uncertainties with regard to the extent of bone regeneration. This technique is expensive and complex. In this study, we examined the bone-inducing ability of uncultured cells of bone marrow aspirate concentrate (BMAC). Material and Method: ß-tricalcium phosphate (ß-TCP) block, 5×5×5mm, with BMAC (BMAC group) or ß-TCP block with nonconcentrated bone marrow aspirate (BMA group) was implanted into the back muscle of beagle dogs. ß-TCP alone was implanted as a control (TCP group). Bone marrow is extracted from the iliac and femur bone. We compared the ability to induce bone formation between the three groups at 3 and 6 weeks after surgery. Histological evaluation was performed in decalcified specimens (HE stain) at two levels of sections per sample. In addition, we compared the number of bone marrow cells that could be cultured for 1 week and collected between the BMAC group and BMA group. We measured the platelet counts, fibrinogen and TGF-ß concentrations of BMAC. We used SEM for morphometric analysis of the implant materials. Next experiment, we evaluated the bone-inducing ability in bone defects (8×7×4mm) of canine mandible. Histological evaluation was performed at 6 and 12 weeks after surgery. Results: The number of bone marrow cells collected from the BMAC group was 4.9-fold those collected from the BMA group. In SEM analysis, the fibrin network of BMAC group was dense than that of BMA group. In ectopic bone formation, average new bone area was 0.79 mm2 and 1.96 mm2 in the BMAC group, 0.06 mm2 and 1.52 mm2 in the BMA group, and 0 mm2 and 0.61 mm2 in the TCP group at 3 and 6 weeks, respectively. Ability of bone formation was significantly higher in the BMAC group than in the TCP group at both 3 and 6 weeks. In the BMA group, ability of bone formation was higher than the TCP groups. In bone defects of mandible, the contour of the alveolar bone crest was well retained in the BMA group and a significant difference was observed between the TCP group and BMA groups at 6 and 12 weeks. Conclusion: In this study, increase of cells from BMA and the importance of fibrin network as scaffold were indicated. These findings indicate that BMAC, which comprises concentrated bone marrow stem cells and a fibrin scaffold that has the ability to induce ectopic bone formation; furthermore, this technique is safe, simple, and useful for bone regeneration in the clinical setting. In our future plan, the optimal type of cells, ECM and growth factors for bone formation in BMA should be investigated. Keywords: bone regeneration, bone marrow aspirate, MSCs