Schwann cell mediated trophic effects by differentiated mesenchymal stem cells
Schwann cell mediated trophic effects by differentiated mesenchymal stem cells
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DOI：
10.1016/j.yexcr.2008.05.013
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发表时间：
2008-08-15
影响因子：
3.7
通讯作者：
Shawcross, Susan G.
中科院分区：
文献类型：
--
作者：
Mahay, Daljeet;Terenghi, Giorgio;Shawcross, Susan G.
从大鼠骨髓中分离出间充质干细胞并进行分化，为周围神经再生提供一种功能替代生长缓慢的雪旺细胞。为了评估分化后的间充质干细胞的特性，将细胞与背根神经节共培养，观察神经营养因子的分泌和神经突的生长情况。与未分化的干细胞相比，与分化干细胞共培养的背根神经节神经元的神经突生长增强。分化的干细胞，如雪旺细胞，负责刺激更长的和分支的神经突。通过酶联免疫吸附试验和阻断抗体，我们已经证明这种作用是由于脑源性神经营养因子和神经生长因子的释放，这两种因子在共培养后分化的间充质干细胞中被上调。选择性酪氨酸激酶抑制剂K252a证实了酪氨酸激酶受体的相关性，当与类似雪旺细胞的分化间质干细胞共培养时，K252a可消除背根神经节神经元的神经突生长。该研究结果进一步支持了间充质干细胞可以分化并表现出与雪旺细胞一样的营养影响的观点。(C) 2008爱思唯尔公司版权所有。
Mesenchymal stem cells were isolated from the bone marrow of rats and differentiated to provide a functional substitute for slow growing Schwann cells for peripheral nerve regeneration. To assess the properties of the differentiated mesenchymal stem cell, the cells were co-cultured with dorsal root ganglia and the secretion of the neurotrophic factors and the neurite outgrowth was evaluated. The neurite outgrowth of the dorsal root ganglia neurons was enhanced in co-culture with the differentiated stem cells compared to the undifferentiated stem cells. Differentiated stem cells like Schwann cells were responsible for the stimulation of longer and branched neurites. Using enzyme-linked immunosorbant assays and blocking antibodies, we have shown that this effect is due to the release of brain derived neurotrophic factor and nerve growth factor, which were up-regulated in differentiated mesenchymal stem cells following co-culture. The relevance of the tyrosine kinase receptors was confirmed by the selective tyrosine kinase inhibitor, K252a which abolished the neurite outgrowth of the dorsal root ganglia neurons when co-cultured with the differentiated mesenchymal stem cells similar to Schwann cells. The results of the study further support the notion that mesenchymal stem cells can be differentiated and display trophic influences as those of Schwann cells. (C) 2008 Elsevier Inc. All rights reserved.