사람 골 형성 단백질 Ex vivo 유전자 치료법을 이용한 척추 유합 = Spinal Fusion Based on Ex Vivo Gene Therapy Using Recombinant Human BMP Adenoviruses

국문 초록 (Abstract)

AdBMP-2와 AdBMP-7을 형질도입 시킨 사람 섬유아세포와 사람 골수기질세포를 면역결핍 생쥐의 척추 옆 근육으로 주입하여 척추 유합을 유도한 결과, AdBMP-7/BMSC가 AdBMP-2/BMSC 또는 AdBMP-7/HuFb와 AdBMP-2/HuFb 보다 골 형성능이 우수하였으며, 척추 유합을 잘 유도하였음을 확인하였다.

다국어 초록 (Multilingual Abstract)

Purpose : Bone morphogenetic proteins (BMPs) play an important role in the formation of cartilage and bone, as well as regulating the growth of chondroblasts and osteoblasts. In this study, we investigated whether recombinant human BMP adenoviruses are available for ex vivo gene therauy, using human fibroblasts and human bone marrow stromal cells in an animal spinal fusion model.
Materials and Methods : Human fibroblasts and human bone marrow stromal cells were transduced with recombinant BMP-2 adenovirus (AdBMP-2) or recombinant BMP-7 adenovirus (AdBMP-7), referred to as AdBMI-7/BMSC, AdBMP-2/BMSC, AdBMP-7/HuFb, and AdBMP-2/HuFb. We showed that each cell secreted active BMPs by alkaline phosphatase staining. Since AdBMP-2 or AdBMP-7 tranducing cells were injected into the paravertebral muscle of athymic nude mice, at 4 weeks and 7 weeks, we confirmed that new bone formation uccurred by induction of spinal fusion on radiographs and histochemical staining.
Results : In the region where the AdBMP-7/BMSC was injected, new bone formation was observed in all cased and spinal fusion was induced in two of these. AdBMP-2/BMSC induced bone formation and spinal fusion occured among one of five. However, in the region where AdBMP/HuFb was injected, neither bone formation nor spinal fusion was observed.
Conclusion : The osteoinductivity of AdBMP-7 was superior to that of AdBMP-2. In addition, The human bone marrow stromal cells were more efficient than the human fibroblasts for bone formation and spinal fusion. Therefore, the results of this study suggest that AdBMP-7/BMSC would be the most useful approach to ex vivo gene therapy for an animal spinal fusion model.