Yeungnam Univ J Med.  2007 Dec;24(2):262-274.

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

• Kim GB
• Kim JR
• Ahn MH
• Seo JS

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.

Keyword

Spine; Spinal fusion; BMP; Gene therapy

MeSH Terms

Adenoviridae*
Alkaline Phosphatase
Animals
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins
Cartilage
Chondrocytes
Fibroblasts
Genetic Therapy*
Humans*
Mesenchymal Stromal Cells
Mice
Mice, Nude
Osteoblasts
Osteogenesis
Spinal Fusion*
Spine
Alkaline Phosphatase
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins