Study of BMP-2 Gene Modified Goat Bone Marrow Stromal Cells in Promoting New Bone Formation

Objective: To evaluate the osteoinductive effects of adenoviral encoding human BMP-2 (AdBMP-2) gene modified goat bone marrow stromal cells (bMSCs) in nude mice. Methods: Primary cultured goat bMSCs were transduced with 50 pfu/ml AdBMP-2 and Ad- LacZ. Gene transfer efficiency was detected by X-gal staining 3 days after AdLacZ gene transduction. AdBMP-2 or AdLacZ gene modified bMSCs were injected into nude mice intramuscularly (number of injection sites: AdBMP-2 = 9; AdLacZ = 9). Three samples in each group were obtained after 2 weeks, and the remaining six were harvested after 4 weeks. All samples were evaluated by histology. MicroCT, BMP-2 immunohistochemistry and X-gal staining were performed for 4-week samples. Results: Gene transfer efficiency reached above 70%. Two weeks after injection into nude mice. AdBMP-2 samples demonstrated a combination of relatively mature bone formation and a lesser amount of cartilaginous tissue. In contrast, only fibroblastic-like tissue was detected in Ad- LacZ-transduced bMSCs samples. At week 4, all six AdBMP-2 sites had new bone formation, while in the AdLacZ group no obvious radiopaque area was detectable by microCT. Histologically, AdBMP-2 transduction induced a large bone mass with fatty marrow tissue. While the AdLacZ group showed mainly fibrotic tissue proliferation, X-gal staining confirmed the bMSCs origin in the AdLacZ group. Conclusion: bMSCs modified with AdBMP-2 gene can promote new bone formation in a nude mice model and could be used for further bone regeneration in the oral and maxillofacial region. Keywords: bone marrow stromal cells, bone morphogenetic protein, gene therapy