Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
Biochem Biophys Res Commun. 2010 Mar 12;393(3):481-6. doi: 10.1016/j.bbrc.2010.02.029. Epub 2010 Feb 10.
Impaired glutamate uptake function of astrocytes associated with accumulation of extracellular glutamate is a well-documented feature of amyotrophic lateral sclerosis (ALS). Enhancing the uptake function of astrocytic glutamate transport 1 (GLT1) may be a potential treatment for this disease. Human adipose-derived stem cells (hADSCs) are capable of secreting a large number of cytokines which exhibit diverse pharmacological effects. Therefore, we investigate the influence of the soluble factors released by hADSCs on the GLT1 in primary astrocytes cultured from SOD1(G93A) mice, a widely studied mutant human SOD1 transgenic model of ALS. Our data indicate that soluble factors from hADSCs significantly upregulate the expression of GLT1 in SOD1(G93A)-bearing astrocytes, which result in enhanced glutamate uptake function. The upregulation of GLT1 is accompanied by the inhibition of caspase-3 activation in mutant astrocytes. In addition, we find that hADSCs cocultured with SOD1(G93A)-bearing astrocytes produce more VEGF, HGF and IGF-1, which are reported to have neuroprotective effects. Our results suggest that hADSCs may be a potential candidate in cellular therapy for ALS.
星形胶质细胞谷氨酸摄取功能受损，导致细胞外谷氨酸积累，这是肌萎缩侧索硬化症（ALS）的一个特征。增强星形胶质细胞谷氨酸转运蛋白 1（GLT1）的摄取功能可能是治疗该病的一种潜在方法。人脂肪源性干细胞（hADSCs）能够分泌大量细胞因子，具有多种药理学作用。因此，我们研究了 hADSCs 释放的可溶性因子对 SOD1(G93A)小鼠原代星形胶质细胞 GLT1 的影响，SOD1(G93A)是一种广泛研究的 ALS 人类 SOD1 突变转基因模型。我们的数据表明，hADSCs 的可溶性因子可显著上调 SOD1(G93A)携带的星形胶质细胞中 GLT1 的表达，从而增强谷氨酸摄取功能。GLT1 的上调伴随着突变星形胶质细胞中 caspase-3 激活的抑制。此外，我们发现与携带 SOD1(G93A)的星形胶质细胞共培养的 hADSCs 产生了更多的 VEGF、HGF 和 IGF-1，这些因子被报道具有神经保护作用。我们的结果表明，hADSCs 可能是 ALS 细胞治疗的潜在候选者。
