Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats

Acta Orthop. 2005 Oct;76(5):637-46. doi: 10.1080/17453670510041709.

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.

Interpretation: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / immunology
  • Animals
  • Antibody Formation
  • Biomechanical Phenomena
  • Bone Marrow Cells / cytology
  • Bone Morphogenetic Proteins / genetics*
  • Cells, Cultured
  • Gene Transfer Techniques*
  • Goats
  • Humans
  • Immunity, Cellular
  • Osteogenesis
  • Tibia / pathology
  • Tibia / physiology
  • Tibia / surgery*
  • Tissue Engineering / methods*
  • Transforming Growth Factor beta*

Substances

  • Bone Morphogenetic Proteins
  • Transforming Growth Factor beta