Mesenchymal Stem Cells Expressing Osteogenic and Angiogenic Factors Synergistically Enhance Bone Formation in a Mouse Model of Segmental Bone Defect
Mesenchymal Stem Cells Expressing Osteogenic and Angiogenic Factors Synergistically Enhance Bone Formation in a Mouse Model of Segmental Bone Defect
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DOI：
10.1038/mt.2009.315
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发表时间：
2010-05-01
影响因子：
12.4
通讯作者：
Ponnazhagan, Selvarangan
中科院分区：
文献类型：
--
作者：
Kumar, Sanjay;Wan, Chao;Ponnazhagan, Selvarangan
间充质干细胞（MSC）在组织再生中的潜力越来越受到人们的关注。现在有越来越多的证据表明MSC对出生后血管发生有重要的贡献。在骨发育和骨折愈合过程中，血管化在骨形成之前被观察到。本研究通过重组腺相关病毒6 （rAAV6）编码骨形态发生蛋白2 （BMP2）和血管内皮生长因子（VEGF），在胸腺裸小鼠胫骨节段性骨缺损小鼠模型中进行体外转导，确定了MSC的潜力。经模拟转导或rAAV6-BMP2: VEGF转导的小鼠MSC在x线片证实截骨后全身移植。通过酶联免疫吸附法测定BMP2和VEGF、双能x线骨密度测定（DXA）、三维微计算机断层扫描（mu CT）测定骨和毛细血管结构、组织形态学测定骨重塑来确定治疗效果。这些分析结果表明，与其他组相比，接受BMP2+ vegf表达MSC的组骨形成增强。治疗效果伴随着血管和成骨细胞生成的增加，这表明它在治疗人类难治性骨不连缺陷时具有有效的潜力。
The potential of mesenchymal stem cells (MSC) in tissue regeneration is increasingly gaining attention. There is now accumulating evidence that MSC make an important contribution to postnatal vasculogenesis. During bone development and fracture healing, vascularization is observed before bone formation. The present study determined the potential of MSC, transduced ex vivo with a recombinant adeno-associated virus 6 (rAAV6) encoding bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) in a mouse model of segmental bone defect created in the tibiae of athymic nude mice. Mouse MSC that were mock-transduced or transduced with rAAV6-BMP2: VEGF were systemically transplanted following radiographic confirmation of the osteotomy. Effects of the therapy were determined by enzyme-linked immunosorbent assay measurements for BMP2 and VEGF, dual-energy X-ray absorptiometry (DXA) for bone density, three-dimensional microcomputed tomography (mu CT) for bone and capillary architecture, and histomorphometry for bone remodeling. Results of these analyses indicated enhanced bone formation in the group that received BMP2+VEGF-expressing MSC compared to other groups. The therapeutic effects were accompanied by increased vascularity and osteoblastogenesis, indicating its potential for effective use while treating difficult nonunion bone defects in humans.