Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats
Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats
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DOI：
10.1016/j.bone.2006.10.030
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发表时间：
2007-04-01
期刊：
影响因子：
4.1
通讯作者：
Lieberman, J. R.
中科院分区：
文献类型：
--
作者：
Hsu, W. K.;Sugiyama, O.;Lieberman, J. R.
本研究的目的是评估通过慢病毒基因转移产生的表达BMP-2的骨髓细胞在大鼠模型中愈合临界尺寸股骨缺损的能力。在刘易斯大鼠的股骨缺损处植入5 × 10（6）个大鼠骨髓基质细胞（RBMSC），所述RBMSC用含有BMP-2基因（组I）、增强型绿色荧光蛋白（LV-GFP）基因（组IV）或仅RBMSC（组V）的慢病毒载体转导。我们还包括感染后8周用慢病毒转导的产生BMP-2的RBMSC治疗的股骨缺损（组III），以及用具有BMP-2基因的慢病毒载体转导的1 × 106个RBMSC的组（组II）。组I中治疗的所有缺损（10/10）在8周时愈合，而对照组（Wand和V组）中无股骨缺损愈合。在第二组中，10个股骨中只有1个。好了Ⅲ组10个股骨中有5个愈合。当与对照组相比时，在组I、II和III中检测到显著更高量的体外BMP-2蛋白产生（p < 0.05）。组织形态学分析显示，与对照样本相比，第I组和第III组的缺损区总骨体积显著更大（p < 0.003）。生物力学测试显示，在峰值扭矩和失效扭矩方面，第I组和第III组中的愈合缺损与完整、未手术股骨相比无显著差异。我们的研究结果表明，通过慢病毒基因转移产生BMP-2的RBMSC具有体外诱导长期蛋白质产生和体内产生大量新骨形成的能力。(c)2007年由Elsevier Inc.出版
The objective of the present study was to assess the ability of bone marrow cells expressing BMP-2 created via lentiviral gene transfer to heal a critical sized femoral defect in a rat model. Femoral defects in Lewis rats were implanted with 5 x 10(6) rat bone marrow stromal cells (RBMSC) transduced with a lentiviral vector containing either the BMP-2 gene (Group I), the enhanced green fluorescent protein (LV-GFP) gene (Group IV), or RBMSC alone (Group V). We also included femoral defects that were treated with BMP-2-producing RBMSC transduced with lentivirus, 8 weeks after infection (Group III), and a group With 1 x 10(6) RBMSC transduced with a lentiviral vector with the BMP-2 gene (Group II). All defects (10/10) treated in Group I healed at 8 weeks compared with none of the femora in the control groups (Groups Wand V). In Group II, only one out of 10 femora. healed. In Group III, 5 out of 10 femora healed. Significantly higher amounts of in vitro BMP-2 protein production were detected in Groups I, II, and III when compared to that of the control groups (p < 0.05). Histomorphometric analysis revealed significantly greater total bone volume in defects in Group I and III when compared to control specimens (p < 0.003). Biomechanical testing revealed no significant differences in the healed defects in Groups I and III when compared to intact, nonoperated femora with respect to peak torque and torque to failure. Our results indicate that BMP-2-producing RBMSC created through lentiviral gene transfer have the capability of inducing long-term protein production in vitro and producing substantial new bone formation in vivo. (c) 2007 Published by Elsevier Inc.