Objective:To compare the ability of three carriers to promote osteogenesis in a mouse model of cell-based gene therapy using BMP-9. Methods:Forty athymic nude mice were randomized into four groups for subcutaneous implantation of carrier and C 2 C 12 cells transfected with adenovirus expressing BMP-9. Each mouse also had a control consisted of carrier with cells infected with adenovirus expressing green fluorescence protein (GFP). One of the four groups had only transfected cells injected subcutaneously with no carrier. The following groups were defined: ① collagen type Ⅰ sponge

② Tri-calcium-phosphate/hydroxy-apatite(HA-TCP)

③Demineralized bone matrix (DBM)

and ④ the subcutaneous injection group.The mice were sacrificed at 4 weeks and plain radiographs obtained. Histologic evaluation of the implantation sites were performed. Results:In the collagen sponge group

9 of 10 (90%)had radiographic evidence of new bone formation

8 of 9(89%)in the HA-TCP group

3 of 6(50%)in the DBM group

and 4 of 9(44%)in the cell-only group. Histologic findings from selected samples included the following:better quality and larger amounts of bone were found in the collagen sponge and HA-TCP samples;a more uniform distribution of cells and bone were noted throughout the collagen sponge samples when compared to the other carriers;a decreased number of cells were noted in DBM samples when compared to the other carriers. Conclusion:Collagen type Ⅰ sponge and HA-TCP carriers consistently produce more bone than DBM carrier in cell-based gene therapy using BMP-9. Addtionally

collagen sponge and HA-TCP provide a better environment for cell based gene therapy as evidenced in the histologic data.