title: Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats.
abstract: BACKGROUND
  Tissue-engineered bone may be used for filling bone defects. There are, however, no reports on this technique used in large animals.
  
  
  METHODS
  We evaluated the effectiveness of, and immune response in repairing diaphyseal bone defects by gene transfer using bone morphogenetic proteins (BMPs). We used adenovirus-mediated human BMP-2 (Adv-hBMP-2) gene-transduced bone marrow stromal cells (BMSCs) to repair 2.1-cm segmental tibial bone defects in goats (group I, n = 7). An Adv-ssgal-transduced BMSC group (group II, n = 5), a non-transduced BMSC group (group III, n = 5), and an untreated group (group IV, n = 2) were used as controls. Self-secreted extracellular matrix was used as cellular carrier.
  
  
  RESULTS
  Radiographic and histomorphometric examination demonstrated more callus in the bone defects of group I compared to other groups. Week 24 after implantation, the defect healing rates of groups I, II, III, and IV were 6/7, 1/5, 2/5, and 0/2, respectively. The maximum compressive strength of new tissue in the bone defects of group I was higher than those of groups II and III. Temporary cellular and persistent humoral immune responses against adenovirus were detected after hBMP-2 gene transfer.
  
  
  CONCLUSIONS
  We found that Adv-hBMP-2 genetransduced BMSCs had superior osteoinductivity in the repair of tibial bone defects in goats, but it could cause temporary cellular and persistent humoral immune responses against adenovirus.
authors.affiliation: Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, P. R. China.
authors.forename: X Leon
authors.initials: XL
authors.lastname: Xu
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Zhen'an
authors.initials: Z
authors.lastname: Zhu
authors.forename: X Edward
authors.initials: XE
authors.lastname: Guo
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Yu
authors.forename: Jueren
authors.initials: J
authors.lastname: Lou
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D001696:Biomechanical Phenomena; D001854:Bone Marrow Cells / Q000166:cytology; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D006041:Goats; D006801:Humans; D007111:Immunity, Cellular; D010012:Osteogenesis; D013977:Tibia / Q000473:pathology / Q000502:physiology / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta