Unique and reliable rat model for the assessment of cell therapy: bone union in the rat mandibular symphysis using bone marrow stromal cells.

Many kinds of bone graft materials have been developed and reported to repair various bone defects. The defects are usually created by surgical resection of pre-existing bone tissue. However, spontaneous healing of bone defects without implantation of materials could be seen, because bone tissue possesses inherent repairing property. The central portion of the lower jaw bone in many animals consists of fibrous tissue and is called the mandibular symphysis. It persists even in old animals and thus can be interpreted as a physiological bone gap or a non-healing bone defect. We implanted calcium phosphate porous ceramics alone or composites of the ceramics and bone marrow stromal cells (BMSCs) into the bone defect (mandibular symphysis) to examine whether it could be filled with new bone tissue, resulting in bone union. Eight weeks after implantation, micro-computed tomography (micro-CT) and histological and biomechanical analyses demonstrated that bone union of the mandibles occurred in all rats with composites but in none of those with ceramics alone. These results showed that the rat mandibular symphysis is a unique bone defect site for the evaluation of bone graft materials. These analyses demonstrated that ceramics alone could not contribute to bone healing in the defect; however, supplementation with BMSCs drastically changed the properties of the ceramics (turning them into osteogenic ceramics), which completely healed the defect. As BMSCs can be culture-expanded using small amounts of bone marrow, the use of the composites might have clinical significance for the reconstruction of various bone tissues, including facial bone.