Effect of Cell-Based VEGF Gene Therapy on Healing of a Segmental Bone Defect
Effect of Cell-Based VEGF Gene Therapy on Healing of a Segmental Bone Defect
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DOI：
10.1002/jor.20658
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发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Schemitsch, Emil H.
中科院分区：
文献类型：
--
作者：
Li, Ru;Stewart, Duncan J.;Schemitsch, Emil H.
骨折愈合需要骨生成和血管生成的协调耦合，其中血管内皮生长因子（VEGF）起着关键作用。我们假设骨折内血管生成和成骨因子的靶向过度表达会通过诱导新血管的发育和刺激/影响骨骼细胞的增殖、存活和活性来促进骨愈合。采用基于细胞的基因转移方法，不使用病毒载体，将5.0 × 10(6)个转染VEGF的成纤维细胞递送至兔胫骨10-mm骨缺损处（组1）（n = 9）；对照组分别给予成纤维细胞（组2）（n = 7）或生理盐水（组3）（n = 7）。12周后，第1组8例胫骨骨折升温，第2组和第3组各4例。在组1中，整个缺损可见骨化；2组和3组缺损呈纤维状，稀疏骨化。1组CD31阳性染色血管多于2组和3组。显微ct三维显示，组1新生骨完全桥接，组2和组3未完全愈合。VEGF治疗组与对照组的显微ct骨结构参数差异有统计学意义（p < 0.05）。这些结果表明，基于细胞的VEGF基因治疗对促进兔长骨节段性缺损的愈合具有显著的血管生成和成骨作用。(C) 2008年中国骨科学会。Wiley期刊公司出版。[J]中华骨科杂志，2009
Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) playsa key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0 x 10(6) fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n = 9); control groups were treated with fibroblasts (Group 2) (n = 7), or saline (Group 3) (n = 7) only. After 12 weeks, eight tibial fractures heated in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group I had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p < 0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:8-14, 2009