骨髄由来間葉系幹細胞(MSCs)を用いた顎裂閉鎖治療法 : MSCsの血管新生に果たす役割の検討

広島大学(Hiroshima University)博士(歯学)Doctor of Philosophy in Dental Sciencedoctora

Bone Regeneration in Artificial Jaw Cleft by Use of Carbonated Hydroxyapatite Particles and Mesenchymal Stem Cells Derived from Iliac Bone

Objectives of the Study. Cleft lip and palate (CLP) is a prevalent congenital anomaly in the orofacial region. Autogenous iliac bone grafting has been frequently employed for the closure of bone defects at the jaw cleft site. Since the related surgical procedures are quite invasive for patients, it is of great importance to develop a new less invasive technique. The aim of this study was to examine bone regeneration with mesenchyme stem cells (MSCs) for the treatment of bone defect in artificially created jaw cleft in dogs. Materials and Methods. A bone defect was prepared bilaterally in the upper incisor regions of beagle dogs. MSCs derived from iliac bone marrow were cultured and transplanted with carbonated hydroxyapatite (CAP) particles into the bone defect area. The bone regeneration was evaluated by standardized occlusal X-ray examination and histological observation. Results. Six months after the transplantation, perfect closure of the jaw cleft was achieved on the experimental side. The X-ray and histological examination revealed that the regenerated bone on the experimental side was almost equivalent to the original bone adjoining the jaw cleft. Conclusion. It was suggested that the application of MSCs with CAP particles can become a new treatment modality for bone regeneration for CLP patients

Dynamic imaging of the effect of mesenchymal stem cells on osteoclast precursor cell chemotaxis for bone defects in the mouse skull

Background/purpose: Mesenchymal stem cells (MSCs) transplantation has previously been used in the field of regenerative medicine. Although bone regeneration is known to occur through the interaction between osteoblasts and osteoclasts, the effect of MSCs on osteoclasts is unknown. Therefore, the purpose of this study was to investigate the effect of MSCs on the chemotaxis of osteoclast precursor cells (RAW264 macrophage cells). Materials and methods: Bone defects were created in mice skulls, and MSCs and a scaffold of carbonated hydroxyapatite were transplanted into the bone defects. RAW264 cells were then transplanted into the mouse tail vein, and their dynamics were observed by an in vivo imaging system. Results: The fluorescent intensity of the MSCs transplant group at the bone defect region was significantly higher on days 3, 5, and 7 compared with the MSCs non-transplant group. Conclusion: Increased RAW264 chemotaxis to the bone defect region occurred following the simultaneous implantation of MSCs in the skull defect. Keywords: Bone regeneration, Chemotaxis, Mesenchymal stem cells, RAW264 cell