Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats.
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.
Xu
X Leon
XL
Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, P. R. China.
Tang
Tingting
T
Dai
Kerong
K
Zhu
Zhen'an
Z
Guo
X Edward
XE
Yu
Chaofeng
C
Lou
Jueren
J
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
D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta