Gene Therapy-Directed Osteogenesis: BMP-7-Transduced Human Fibroblasts Form Bonein Vivo

Osteoinduction by ex vivo adenovirus-mediated BMP2 delivery is independent of cell type

“…11 Our study also indicates that transduced human cells do not differentiate along a chondro-osseous pathway and do not incorporate into the newly formed cartilage or bone. This conclusion differs from those of several studies, 4,8,9 although orthotopic rather than heterotopic bone was analyzed. The fact that several cell types can be transduced and elicit bone formation also argues against Adenovirus BMP2-induced bone formation Z Gugala et al a major contribution of the transduced cells as constituents of these new tissues.…”

“…4,8,9,18 In our study, cells were injected without carrier or scaffold, whereas in all other studies collagen carriers were utilized. 4,8,9,18 Presumably, the carrier immobilizes the cells, decreasing their clearance rate. Additionally, the carrier may also retain high amounts of BMP2, forcing bone formation within the carrier, which can result in juxtaposition of the transduced cells and the new bone.…”

“…[1][2][3][4][5][6][7][8] Localized delivery of cells transduced ex vivo with adenoviral vectors encoding bone morphogenetic proteins (BMPs) has proven successful in induction of new bone formation in hetero-and orthotopic locations. Although safe and efficacious gene-based bone induction systems have yet to be developed, the adenoviral delivery of BMP offers the potential of rapidly achieving local effective concentrations of the protein to induce bone formation.…”

Ex vivo gene therapy with stromal cells transduced with a retroviral vector containing the BMP4 gene completely heals critical size calvarial defect in rats

“…Although there are several studies which have shown evidence for skeletal regeneration in vivo using ex vivo modified stromal cells, myoblasts, or fibroblasts, 10,15,16,22,24,25 our study is unique in that it provides quantitative data on the extent of healing by valid bone density measurements. Furthermore, our data demonstrate that the healing of a critical calvarial defect is dependent on the time of exposure, as well as the number of BMP4-expressing stromal cells implanted.…”

“…21 (2) It has recently been shown that implantation of gingival fibroblasts transduced with a BMP7 adenoviral vector in rats 22 or autologous stromal cells transduced with a BMP7 MLV-based vector in rabbits 20 was able to heal cranial bone defects within 4 weeks and 12 weeks, respectively. (3) The management of the surgical site is relatively easy.…”