Induction of glial glutamate transporters in adult mesenchymal stem cells
Induction of glial glutamate transporters in adult mesenchymal stem cells
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DOI：
10.1111/j.1471-4159.2004.02709.x
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发表时间：
2004-10-01
影响因子：
4.7
通讯作者：
Hermans, E
中科院分区：
文献类型：
--
作者：
de Hemptinne, I;Vermeiren, C;Hermans, E
成人骨髓间充质干细胞是一种多能细胞，可分化为多种中胚层组织。最近的研究报道了它们也能够进化成非中胚层细胞，特别是神经细胞。虽然大多数这些研究表明，操纵这些细胞触发典型的神经元标记物的表达，较少被称为诱导神经元或神经胶质相关的生理特性。本研究的重点是谷氨酸转运蛋白的表达和活性在培养条件下生长的大鼠间充质干细胞有利于他们分化为星形胶质细胞的特性。发现细胞暴露于培养补充物G5十天增加了巢蛋白（神经上皮干细胞中间丝）的表达，巢蛋白是一种由神经干细胞表达的中间丝蛋白。同时，通过RT-PCR和免疫细胞化学检测到高亲和力谷氨酸转运蛋白GLT-1（和GLAST）表达的强烈诱导。这种表达与Na+依赖性[H-3] D-天冬氨酸摄取的显著增加相关。最后，虽然不能检测到胶质细胞酸性蛋白的免疫反应性，但证明了星形胶质细胞酶谷氨酰胺合成酶的诱导表达。这些结果表明，在体外分化的成体间充质干细胞的神经前体与功能性谷氨酸转运系统的诱导相一致。虽然这些细胞的星形胶质细胞的性质仍有待证实，这一观察结果支持间充质干细胞作为一种有前途的工具，用于治疗神经系统疾病，涉及谷氨酸兴奋性的研究。
Adult bone marrow mesenchymal stem cells are multipotent cells that can differentiate into a variety of mesodermal tissues. Recent studies have reported on their ability to also evolve into non-mesodermal cells, especially neural cells. While most of these studies revealed that manipulating these cells triggers the expression of typical neurone markers, less is known about the induction of neuronal- or glial-related physiological properties. The present study focused on the characterisation of glutamate transporters expression and activity in rat mesenchymal stem cells grown in culture conditions favouring their differentiation into astroglial cells. Ten days exposure of the cells to the culture supplement G5 was found to increase the expression of nestin (neuro-epithelial stem cell intermediate filament), an intermediate filament protein expressed by neural stem cells. Simultaneously, a robust induction of the high-affinity glutamate transporter GLT-1 (and GLAST) expression was detected by RT-PCR and immunocytochemistry. This expression was correlated with a highly significant increase in the Na+-dependent [H-3]D-aspartate uptake. Finally, while glial fibrillary acidic protein immunoreactivity could not be detected, the induced expression of the astrocytic enzyme glutamine synthetase was demonstrated. These results indicate that in vitro differentiation of adult mesenchymal stem cells in neural precursors coincides with the induction of functional glutamate transport systems. Although the astrocytic nature of these cells remains to be confirmed, this observation gives support to the study of mesenchymal stem cells as a promising tool for the treatment of neurological diseases involving glutamate excitoxicity.