Osteogenic Potential of the Osteogenic Matrix Cell Sheets in Maxillofacial Regeneration

Regeneration of maxillofacial bone defects such as maxillary alveolar clefts and bone resorption resulting from marginal periodontitis pose a significant clinical challenge. We focused on the new cell transplantation technique in which bone marrow-derived mesenchymal stem cells (BMSCs) were cultured as cell sheets with osteogenic potential (designated osteogenic matrix sheets). This study was performed to evaluate the usefulness of the osteogenic matrix cell sheets in maxillofacial regeneration, using the mandibular nonunion model in rats.

We obtained bone marrow cells by flushing out the femoral shafts of 7 week-old male Fischer 344 rats with medium. The released cells were collected in the culture flasks containing regular medium supplemented with 15% fetal bovine serum and cultured. After reaching confluence, the primary cultured cells were released from the culture substratum using trypsin–EDTA. To prepare osteogenic matrix cell sheets, released cells were subcultured with osteoinductive medium until confluence and lifted as a cell sheet using a scraper. Different from human mandible, rat mandible is formed by a paired bone and the central portion consists of fibrous tissue. Therefore it is interpreted as a nonunion bone defect. For implantation, we made the bone defect by curetting the fibrous tissue in the central portion of the rat mandible. In the experimental group (five rats), the defects were filled with the osteogenic matrix cell sheets. In the control group (five rats), the mandibles were sham-operated. Eight weeks after implantation, micro computed tomography and histological analyses were taken.

Both analyses demonstrated that bone union of the mandible occurred in all rats of experimental group, but in none of those of control group.

These results suggest that the osteogenic matrix cell sheets may regenerate the maxillofacial bone. The characteristics of maxillofacial bone defects are small and low load-bearing, but are quite complicated, especially compared with bone defects in the orthopedic surgery field. The osteogenic matrix cell sheets are characterized by a good operability and shaping property, thus they may be an optimal application for maxillofacial regeneration.

References

1) T Yagyuu, T Kirita, K Hattori, et al.: Unique and reliable rat model for the assessment of cell therapy: bone union in the rat mandibular symphysis using bone marrow stromal cells. J Tissue Eng Regen Med 2012

2) M Akahane, A Nakamura, H Ohgushi, et al.: Osteogenic matrix sheet-cell transplantation using osteoblastic cell sheet resulted in bone formation without scaffold at an ectopic site-. J Tissue Eng Regen Med 2: 196, 2008