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영남의대학술지 Vol.24 No.2 p262-274, Dec. 2007

Original Article

사람 골 형성 단백질 Ex vivo 유전자 치료법을 이용한 척추 유합

Spinal Fusion Based on Ex Vivo Gene Therapy Using Recombinant Human BMP Adenoviruses

김기범, 김재룡*, 안면환†?서재성†

영남대학교 의과대학 의학과, 영남대학교 의과대학 생화학?분자생물학교실*, 정형외과학교실†

책임저자：안면환, 대구광역시 남구 대명5동 317-1, 영남대학교 의과대학 정형외과학교실

Tel: (053) 620-3643, Fax: (053) 628-4020

E-mail: mwahn@med.yu.ac.kr

December 30, 2007

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 therapy, 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 AdBMP-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 occurred 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 cases and spinal fusion was induced in two of these. AdBMP-2/BMSC induced bone formation and spinal fusion occurred 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.

본 논문은 2004년도 영남대학 의과대학의 학생연구비의 지원을 받아 이루어졌음.

Key Words: Spine, Spinal fusion, BMP, Gene therapy

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