Quantitative, structural, and image-based mechanical analysis of nonunion fracture repaired by genetically engineered mesenchymal stem cells.
Quantitative, structural, and image-based mechanical analysis of nonunion fracture repaired by genetically engineered mesenchymal stem cells.
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DOI：
10.1016/j.jbiomech.2010.04.031
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发表时间：
2010-08-26
影响因子：
2.4
通讯作者：
Gazit, Dan
中科院分区：
文献类型：
--
作者：
Kallai, Ilan;van Lenthe, G. Harry;Ruffoni, Davide;Zilberman, Yoram;Muller, Ralph;Pelled, Gadi;Gazit, Dan
关键词：
干细胞介导的骨折修复基因治疗利用基因工程的间充质干细胞（MSCs）诱导骨生长，被认为是骨骼组织再生的有前途的方法。先前的研究表明，小鼠骨折不愈合可以通过植入过表达重组人骨形态发生蛋白-2（rhBMP-2）的MSC来修复。在桡骨骨折部位由MSC诱导的骨组织的纳米压痕研究表明，与处理后8周的完整鼠骨相比，具有相似的弹性模量。在本研究中，我们试图研究骨髓间充质干细胞植入后修复的小鼠桡骨的微结构和生物力学特性的时间变化。MSC植入后10周和35周进行高分辨率显微计算机断层扫描（Micro-CT），然后进行显微有限元（Micro-FE）分析。结果表明，随着时间的推移，再生的骨组织重塑，如骨体积、总体积和连接密度的显著减少以及矿物质密度的增加所示。此外，在治疗后10周和35周，用MSC修复的肢体的轴向刚度比对侧完整肢体高2至1.5倍。这些结果可归因于尺骨和桡骨之间发生的融合。总之，虽然MSC诱导骨形成，这超过了骨折部位，随着时间的推移，修复骨痂发生显着重塑。此外，用MSC移植物治疗的肢体表现出优越的上级生物力学性能，这可能表明MSC在骨折不愈合修复中的未来应用的临床益处。
Stem cell-mediated gene therapy for fracture repair, utilizes genetically engineered mesenchymal stem cells (MSCs) for the induction of bone growth and is considered a promising approach in skeletal tissue regeneration. Previous studies have shown that murine nonunion fractures can be repaired by implanting MSCs over-expressing recombinant human bone morphogenetic protein-2 (rhBMP-2). Nanoindentation studies of bone tissue induced by MSCs in a radius fracture site indicated similar elastic modulus compared to intact murine bone, eight weeks post treatment. In the present study we sought to investigate temporal changes in microarchitecture and biomechanical properties of repaired murine radius bones, following the implantation of MSCs. High resolution micro computed tomography (Micro-CT) was performed 10 and 35 weeks post MSC implantation, followed by micro finite element (Micro-FE) analysis. The results have shown that the regenerated bone tissue remodels over time, as indicated by a significant decrease in bone volume, total volume and connectivity density combined with an increase in mineral density. In addition, the axial stiffness of limbs repaired with MSCs was 2 to 1.5 times higher compared to the contralateral intact limbs, at 10 and 35 weeks post treatment. These results could be attributed to the fusion that occurred between in the ulna and radius bones. In conclusion, although MSCs induce bone formation, which exceeds the fracture site, significant remodeling of the repair callus occurs over time. In addition, limbs treated with an MSC graft demonstrated superior biomechanical properties, which could indicate the clinical benefit of future MSC application in nonunion fracture repair.
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影响因子：
4.1
作者：
Hsu, W. K.;Sugiyama, O.;Lieberman, J. R.
通讯作者：
Lieberman, J. R.
影响因子：
6.2
作者：
Hildebrand, T;Laib, A;Rüegsegger, P
通讯作者：
Rüegsegger, P
影响因子：
2.4
作者：
Kabel, J;van Rietbergen, B;Huiskes, R
通讯作者：
Huiskes, R
影响因子：
4.1
作者：
Müller, R;Van Campenhout, H;Rüegsegger, P
通讯作者：
Rüegsegger, P
影响因子：
2.8
作者：
Lieberman, JR;Le, LQ;Stevenson, O
通讯作者：
Stevenson, O