VEGF-165基因修饰的骨髓间充质干细胞移植修复犬股骨头坏死

目的研究hVEGF-165基因转染的犬骨髓间充质干细胞移植修复自体股骨头坏死的效果。方法用股骨颈截骨后克氏针再固定的方法建立犬股骨头坏死的动物模型,分为转基因间充质干细胞移植组、单纯间充质干细胞移植组和未治疗组,每组9只动物(18侧髋关节)。脂质体法将hVEGF-165基因转染进入骨髓间充质干细胞。造模后10周经大转子将细胞植入股骨头坏死区,转基因间充质干细胞和未转基因干细胞随机植入同一动物的左侧或右侧后肢。细胞移植后第2、8和12周取股骨头标本进行骨小梁定量分析,结合X线和同位素断层扫描分析3组间成骨修复的差别,并比较第12周时各组标本中截骨平面以上的血管数。结果①造模手术后10周,手术侧股骨颈骨折已愈合,但股骨头均出现典型的坏死。②骨小梁定量分析提示,在每一个时间点各组的成骨修复的差别有统计学意义:转基因间充质干细胞移植组的成骨修复好于单纯干细胞移植,未治疗组最差。X线和SPECT的表现与此相符。③12周时,转基因间充质干细胞移植组中血管数量最多,间充质干细胞移植组与未治疗组的血管数量没有统计差别。结论与未转基因的间充质干细胞移植相比,转染hVEGF-165基因后的间充质干细胞移植能够增加股骨头坏死区血管...

Treatment of osteonecrosis of the femoral head with hVEGF-165-gene- modified mesenchymal stem cells in mongrel dogs

Purpose The efficacy of hVEGF-165-gene-modified mesenchymal stem cells(MSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in mongrel dogs.Methods Animal model was surgically induced by neck osteotomy and repinning to make a model of osteonecrosis of femoral head.Twenty-seven dogs(54 hips)were divided into three equal-sized groups:a hVEGF-165 gene transfected MSCs-implanted group,an MSCs-transplanted group,and an untreated group.Lipofectin method was used to introduce hVEGF-165 gene into mesenchymal stem cells.Gene-transfected and non-transfected MSCs were implanted into the same animal's left or right femoral head seperately and randomly.Bone and blood vessel formation were determined qualitatively and quantitatively by methods including histology,imageology,histomorphometry and immunofluorescent analysis.Results Healing of the femoral neck fracture occurred and the regions of histologically evident osteonecrosis were successfully produced ten weeks after the operation.The difference in vWF expression was statistically significant between the hVEGF-165-gene-modified MSCs-implanted group and the other two groups.Histomorphometric analysis showed that the implantation of hVEGF-165-gene-modified MSCs resulted in a significant increase in the quantity of regenerated bone compared with that of MSCs alone at all time-points.Conclusions This study demonstrates that the number of blood vessels in the necrotic area rises after the transplantation of hVEGF-165-gene-modified MSCs,which contributes to better repair process than that occurred in MSCs-transplanted group.