Effects of Allogenous Periosteal-Derived Cells Transfected With Adenovirus-Mediated BMP-2 on Repairing Defects of the Mandible in Rabbits

• Published in: Journal of oral and maxillofacial surgery Vol. 71; no. 10; pp. 1789 - 1799
• Main Authors: Sun, Mingxia, MD, Tan, Wanye, PhD, Wang, Ketao, PhD, Dong, Zuoqing, PhD, Peng, Huahai, MD, Wei, Fengcai, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013
• Subjects: Adenoviridae - genetics; Alkaline Phosphatase - analysis; Animals; Bone Morphogenetic Protein 2 - therapeutic use; Bone Regeneration - genetics; Bone Substitutes - chemistry; Cell Culture Techniques; Cell Proliferation; Cell Transplantation; Ceramics - chemistry; Coloring Agents; Dentistry; Enzyme-Linked Immunosorbent Assay; Genetic Vectors - genetics; Guided Tissue Regeneration - methods; Humans; In Situ Hybridization; Mandibular Diseases - surgery; Osteogenesis - physiology; Periosteum - cytology; Rabbits; Recombinant Proteins - therapeutic use; Surgery; Tetrazolium Salts; Thiazoles; Tissue Engineering - methods; Tissue Scaffolds; Transfection; Transforming Growth Factor beta - therapeutic use; Transplantation, Homologous
• ISSN: 0278-2391; 1531-5053
• DOI: 10.1016/j.joms.2013.03.007

Purpose This report describes the effect of periosteal-derived cells transfected with adenovirus-mediated bone morphogenetic protein-2 (BMP-2) on the repair of mandibular defects in rabbits. Materials and Methods Periosteal-derived cells were transfected with a replication-defective adenoviral vector encoding BMP-2, and the expression of BMP-2 was examined in transfected cells using in situ hybridization and enzyme-linked immunosorbent assay. In addition, the proliferation ability and activity of alkaline phosphatase of transfected cells were examined using the 3-[4,5-dimethylthiazol-2-Yl]-2,5-diphenyltetrazolium bromide method and enzymology, respectively. In vitro critical-size defects (about 10 × 6 mm) were made bilaterally in each rabbit mandible, and individual sites were implanted with tissue-engineered bone modified with an adenovirus construct encoding the recombinant human BMP-2 gene (Ad-BMP-2), tissue-engineered bone without modification, single bioactive glass ceramic, or no implants (control). New bone formation was evaluated by histochemical stain. Results BMP-2 expression in the supernate of infected cells was detected from the first day after Ad-BMP-2 transfection and remained at a high level for at least 2 weeks. Alkaline phosphatase expression in transfected cells was significantly greater than in uninfected cells. The group of Ad-BMP-2–modified periosteal-derived cells formed more new bone than the other group at any time point. Conclusion Gene-modified tissue-engineered bone grafts have greater osteogenic potential than single tissue-engineered bone and single bioactive glass ceramic graft. Ex vivo Ad-BMP-2 transfer to periosteal-derived cells can increase bone formation in critical-size bone defects. Further studies are needed to determine if modified engineered cells can be developed for safe and effective clinical applications.