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脑内微量注射人骨髓间充质干细胞可减轻神经病理性痛小鼠的痛觉过敏。

Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice.

机构信息

Division of Pharmacology L. Donatelli, Department of Experimental Medicine, Second University of Naples, 80138 Naples, Italy.

出版信息

Cell Mol Life Sci. 2010 Feb;67(4):655-69. doi: 10.1007/s00018-009-0202-4. Epub 2009 Nov 24.

Abstract

Neuropathic pain is a very complex disease, involving several molecular pathways. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. We used spared nerve injury model of neuropathic pain to assess the possible use of human mesenchymal stem cells (hMSCs) as anti-neuropathic tool. Human MSCs were transplanted in the mouse lateral cerebral ventricle. Stem cells injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored 7, 10, 14, 17, and 21 days after surgery. hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once transplanted in cerebral ventricle. Anti-nociceptive effect was detectable from day 10 after surgery (6 days post cell injection). Human MSCs reduced the mRNA levels of the pro-inflammatory interleukin IL-1beta mouse gene, as well as the neural beta-galactosidase over-activation in prefrontal cortex of SNI mice. Transplanted hMSCs were able to reduce astrocytic and microglial cell activation.

摘要

神经病理性疼痛是一种非常复杂的疾病,涉及多个分子途径。目前可用的药物通常不是针对疼痛产生和传播的几个机制起作用的。我们使用 spared nerve injury 模型的神经病理性疼痛来评估人骨髓间充质干细胞 (hMSCs) 作为抗神经病理性工具的可能用途。人 MSCs 被移植到小鼠侧脑室。坐骨神经手术后 4 天进行干细胞注射。手术后 7、10、14、17 和 21 天监测神经病理性小鼠。hMSCs 一旦被移植到脑室,就能够减轻疼痛样行为,如机械性痛觉过敏和热痛觉过敏。术后 10 天(细胞注射后 6 天)即可检测到抗伤害作用。hMSCs 降低了促炎白细胞介素 IL-1beta 基因在 SNI 小鼠前额叶皮层中的 mRNA 水平,以及神经 β-半乳糖苷酶的过度激活。移植的 hMSCs 能够减少星形胶质细胞和小胶质细胞的激活。

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