Bone Morphogenetic Protein-Transduced Human Fibroblasts Convert to Osteoblasts and Form Bone in Vivo

Experimental cell or ex vivo gene therapy for localized bone formation typically uses osteoprogenitor cells propagated from periosteum or bone marrow. Both require bone or marrow biopsies to obtain cells. We have demonstrated that implantation of gingival or dermal fibroblasts transduced with BMP ex vivo, using a recombinant adenovirus (AdCMVBMP) attached to porous biodegradable scaffolds, form bone in vivo. Here we show that BMP-7-transduced fibroblasts suspended in injectable thermoset hydrogels form complete ossicles on subcutaneous injection and repair segmental defects in rat femurs. Bone formation was preceded by an intermediate cartilage stage. To determine the fate of the implanted transduced cells, thermoset hydrogel suspensions of ex vivo BMP-7-transduced or nontransduced fibroblasts were placed in diffusion chambers and implanted to allow development in vivo without direct contact with host cells. Only the BMP-transduced fibroblasts formed bone within the diffusion chambers in vivo, revealing that BMP transduction induces osteoblastic conversion of these cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63216/1/107632702760184709.pd

Molecular Lysis of Synovial Lining Cells by In Vivo Herpes Simplex Virus-Thymidine Kinase Gene Transfer

Overview summary Previous studies have shown that synovial lining cells are susceptible to in vivo transfection using purified expression plasmid DNA. Roessler et al. now report on the use of a plasmid that mediates transient overexpression of herpes simplex virus thymidine kinase to transfect synovial lining cells in an animal model of proliferative inflammatory arthritis. After in vivo intraarticular transfection using the pNGVL-TK expression plasmid, the animals were treated with intravenous ganciclovir for a period of 3 days. They report that examination of the synovial tissues 21 days after completion of the gene therapy showed evidence of cytolysis that was confined to the synovial lining cells within inflamed synovium. No evidence of cytolysis or necrosis was observed in articular cartilage present within the treated joints. Similar methods to achieve a molecular lysis of the synovial lining layer may have applicability to the treatment of human inflammatory arthritis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63330/1/hum.1998.9.18-2735.pd