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

Abstract

(2005) Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats, Acta Orthopaedica, 76:5, 637-646, DOI: 10.1080 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.

Lentiviral-mediated gene transfer into human adipose-derived stem cells: role of NELL1 versus BMP2 in osteogenesis and adipogenesis <italic>in vitro</italic>

“…Although adenoviral-mediated NELL1 gene therapy has been demonstrated to be effective in promoting bone regeneration, these experiments were performed mainly in small animal models [13][14][15]. Since adenoviral vectors predominantly persist as episomal DNA molecules in the host cell, the target genes cannot be expressed over the long term [17][18][19]. Thus, in the repair of bone defects in large animals or humans via adenovirus-mediated gene transfer, NELL1 cannot be persistently delivered to induce sufficient osteogenesis.…”

Gene therapy for the regeneration of bone

“…The traditional ex vivo approach using Ad.BMP-2 has given highly encouraging results in horses 32 , goats 15, 65, 72 and pigs 12 .…”

Healing of massive segmental femoral bone defects in minipigs by allogenic ASCs engineered with FLPo/Frt-based baculovirus vectors

“…However, injection of AdBMP2 into the iliac crest defects of the pelvic bone of white mountain sheep elicited antibodies against adenovirus and BMP2, which impaired the bone formation and subsequent healing [52]. Moreover, implantation of BMSCs engineered with AdBMP2 into segmental tibial defects in goats concomitantly provoked temporary cellular and persistent humoral immune responses against adenovirus that impeded the healing [53]. Although baculovirus transduction of human BMSCs elicited toll-like receptor 3 pathway [54], implantation of the hybrid baculovirus-engineered pASCs into minipigs only evoked transient antibody, cytokine and local cellular immune responses stemming from the implantation procedure [50].…”