Transplantation of bone marrow stromal cells for peripheral nerve repair
Transplantation of bone marrow stromal cells for peripheral nerve repair
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DOI：
10.1016/j.expneurol.2006.12.004
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发表时间：
2007-03-01
影响因子：
5.3
通讯作者：
Hsu, Shan-Hui
中科院分区：
文献类型：
--
作者：
Chen, Chun-Jung;Ou, Yen-Chuan;Hsu, Shan-Hui
利用骨髓基质细胞（BMSCs）进行细胞移植治疗神经功能缺损已成为近年来再生医学研究的热点。有证据表明，各种生长促进物质的分泌可能在神经系统疾病的功能恢复中发挥重要作用。为了确定骨髓间充质干细胞再生潜力的可能机制，本研究在大鼠坐骨神经缺损15 mm模型中研究了神经营养因子的产生和可能的贡献。体外培养的骨髓间充质干细胞形态均匀，呈成纤维细胞样。我们提供了一些证据来证明移植成纤维细胞样骨髓间充质干细胞对坐骨神经再生的有益作用。与硅胶管对照动物相比，这种处理导致(i)通过足迹分析改善了行走行为，（ii）减少了腓肠肌重量和肌电图大小的损失，（iii）试管内再生轴突的数量更多。培养的成纤维细胞样骨髓间充质干细胞组成性地表达营养因子和支持物质，包括神经生长因子（NGF）、脑源性神经营养因子（BDNF）、胶质细胞系源性神经营养因子（GDNF）、睫状体神经营养因子（CNTF）、胶原蛋白、纤维连接蛋白和层粘连蛋白。骨髓间充质干细胞移植后的再生过程在早期和后期都伴随着神经营养因子的表达升高。这些结果结合在一起，再加上记录在案的雪旺细胞样分化，提供了证据表明神经营养因子的产生与植入骨髓间充质干细胞的再生潜力密切相关。(c) 2006爱思唯尔公司版权所有。
Cell transplantation using bone marrow stromal cells (BMSCs) to alleviate neurological deficits has recently become the focus of research in regenerative medicine. Evidence suggests that secretion of various growth-promoting substances likely plays an important role in functional recovery against neurological diseases. In an attempt to identify a possible mechanism underlying the regenerative potential of BMSCs, this study investigated the production and possible contribution of neurotrophic factors by transected sciatic nerve defect in a rat model with a 15 mm gap. Cultured BMSCs became morphologically homogeneous with fibroblast-like shape after ex vivo expansion. We provided several pieces of evidence for the beneficial effects of implanted fibroblast-like BMSCs on sciatic nerve regeneration. When compared to silicone tube control animals, this treatment led to (i) improved walking behavior as measured by footprint analysis, (ii) reduced loss of gastrocnemius muscle weight and EMG magnitude, and (iii) greater number of regenerating axons within the tube. Cultured fibroblast-like BMSCs constitutively expressed trophic factors and supporting substances, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), collagen, fibronectin, and laminin. The progression of the regenerative process after BMSC implantation was accompanied by elevated expression of neurotrophic factors at both early and later phases. These results taken together, in addition to documented Schwann cell-like differentiation, provide evidence indicating the strong association of neurotrophic factor production and the regenerative potential of implanted BMSCs. (c) 2006 Elsevier Inc. All rights reserved.