骨形态发生蛋白2基因转染的骨髓间充质干细胞修复羊胫骨干骨缺损

Repair of the segmental tibial bone defects in goat by BMP-2 gene transferred bone marrow derived mesenchymal stem cell

目的评价腺病毒介导的人骨形态发生蛋白2(Adv-hBMP-2)基因转染的羊骨髓间充质干细胞(BMSCs)对长骨干骨缺损的修复效果。方法22只羊,体重18.1～29.5kg。制造羊胫骨干骨缺损(2.1cm),分为4组Ⅰ组,Adv-hBMP-2转染BMSCs组(8只);Ⅱ组,腺病毒介导的β半乳糖苷酶(Adv-βgal)转染BMSCs组(6只);Ⅲ组,未转染BMSCs组(6只);Ⅳ组,未治疗组(2只)。细胞自身分泌的细胞外基质作为细胞载体。分期行X线、计量组织学检查和生物力学测定。结果X线检查示Ⅰ组的羊胫骨干骨缺损内有明显骨痂形成;24周,Ⅰ、Ⅱ、Ⅲ和Ⅳ组的愈合率分别为6/7、1/5、2/5及0/1,X线疗效评分显示Ⅰ组与Ⅱ、Ⅲ组的评分比较,差异有显著性意义。组织学检查显示,与其它组相比,Ⅰ组的新生骨量最多,并有皮质骨形成。生物力学测试示Ⅰ组的力学强度最大。结论Adv-hBMP-2基因转染的BMSCs在缺乏骨传导性支架的条件下可修复长骨干骨缺损。

Objective To evaluate effectiveness of bone marrow derived mesenchymal stem cells(BMSCs) transduced by adenovirus mediated human bone morphogenetic protein-2 (Adv-hBMP-2) gene in the repair of diaphysic segmental bone defects of goats. Methods The tibial bone defects (2.1 cm) of 22 goats, who weighted from 18.1 kg to 29.5 kg, were established and divided into 4 groups: groupⅠ, Adv-hBMP-2 transduced BMSCs group (n=8); groupⅡ, adenovirus mediated β-galactosidase(Adv-βgal)gene transduced BMSCs group (n=6); groupⅢ, non-transduced BMSCs group (n=6); groupⅣ, untreated group (n=2). Roentgenography, histomorphometrical analysis and biomechanical measurement were studied at various times. Results Roentgenography showed more callus in the bone defect site of group Ⅰ. At 24th week after implantation, the healing rates of group Ⅰ,Ⅱ,Ⅲ, and Ⅳ were 6/7, 1/5, 2/5, and 0/1 respectively. There was statistic significant difference of X-ray grading between groupⅠand groupⅡor Ⅲ. Histomorphometrical analysis showed much more total new trabecular bone area (TBA) of groupⅠthan that of other groups. Biomechanical strength of groupⅠwas superior to that of groupⅡand Ⅲ. Conclusion Adenovirus mediated BMP-2 gene transferred BMSCs can repair segmental bone defect in goat without osteoconductive scaffold.