Department of Pathology, The University of Alabama, Birmingham, Alabama35294-0007, USA.
Mol Ther. 2010 May;18(5):1026-34. doi: 10.1038/mt.2009.315. Epub 2010 Jan 12.
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 (microCT) 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.
间充质干细胞（MSC）在组织再生中的潜力越来越受到关注。越来越多的证据表明，MSC 对出生后的血管生成有重要贡献。在骨骼发育和骨折愈合过程中，在骨形成之前就观察到了血管化。本研究在无胸腺裸鼠的胫骨中建立节段性骨缺损的小鼠模型，确定了经重组腺相关病毒 6（rAAV6）转导编码骨形态发生蛋白 2（BMP2）和血管内皮生长因子（VEGF）的 MSC 的潜力。在影像学确认截骨术后，对 mock 转导或 rAAV6-BMP2:VEGF 转导的 MSC 进行系统移植。通过酶联免疫吸附测定（ELISA）测量 BMP2 和 VEGF、双能 X 射线吸收法（DXA）测量骨密度、三维微计算机断层扫描（microCT）测量骨和毛细血管结构以及组织形态计量学测量骨重塑来确定治疗效果。这些分析的结果表明，与其他组相比，接受 BMP2+VEGF 表达 MSC 的组的骨形成增强。治疗效果伴随着血管生成和成骨细胞生成的增加，表明其在治疗人类难治性骨不连骨缺损方面具有潜在的有效应用。
