Human mesenchymal stromal cell transplantation modulates neuroinflammatory milieu in a mouse model of amyotrophic lateral sclerosis
Human mesenchymal stromal cell transplantation modulates neuroinflammatory milieu in a mouse model of amyotrophic lateral sclerosis
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DOI：
10.1016/j.jcyt.2014.02.003
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发表时间：
2014-08-01
期刊：
影响因子：
4.5
通讯作者：
Vercelli, Alessandro
中科院分区：
文献类型：
--
作者：
Boido, Marina;Piras, Antonio;Vercelli, Alessandro
背景目标。间充质基质细胞（MSC）经过实质内、鞘内和静脉内给药后，先前已在 SOD1（超氧化物歧化酶 1）小鼠的肌萎缩侧索硬化症中进行了细胞治疗测试。然而，每种给药途径都有特定的优点和缺点。方法。我们在 SOD1 G93A 小鼠症状最早出现时，将人间充质干细胞 (hMSC) 注入到 SOD1 G93A 小鼠的腰池中，该腰池易于接近，可用于门诊手术。对照动物接受盐水注射。从2个月大开始检查小鼠的运动行为，直至处死小鼠。移植后2周处死动物；对腰椎运动神经元进行体视计数，在免疫组织化学后对星形胶质细胞和小胶质细胞进行分析和定量，并通过实时聚合酶链反应测定细胞因子的表达。结果。我们提供的证据表明这种给药途径可以发挥强烈的积极作用。运动神经元死亡和运动衰退被延迟，星形胶质细胞增生减少，小胶质细胞激活受到调节。此外，与野生型相比，hMSC移植阻止了在盐水处理的转基因小鼠中观察到的抗炎白细胞介素10和血管内皮生长因子的下调，并导致抗炎白细胞介素13的表达显着增加。结论。我们的结果表明，hMSCs 在脑池内给药时，可以发挥其旁分泌潜力，影响宿主的炎症反应。
Background aims. Mesenchymal stromal cells (MSCs), after intraparenchymal, intrathecal and endovenous administration, have been previously tested for cell therapy in amyotrophic lateral sclerosis in the SOD1 (superoxide dismutase 1) mouse. However, every administration route has specific pros and cons. Methods. We administrated human MSCs (hMSCs) in the cisterna lumbaris, which is easily accessible and could be used in outpatient surgery, in the SOD1 G93A mouse, at the earliest onset of symptoms. Control animals received saline injections. Motor behavior was checked starting from 2 months of age until the mice were killed. Animals were killed 2 weeks after transplantation; lumbar motoneurons were stereologically counted, astrocytes and microglia were analyzed and quantified after immunohistochemistry and cytokine expression was assayed by means of real-time polymerase chain reaction. Results. We provide evidence that this route of administration can exert strongly positive effects. Motoneuron death and motor decay were delayed, astrogliosis was reduced and microglial activation was modulated. In addition, hMSC transplantation prevented the downregulation of the anti-inflammatory interleukin-10, as well as that of vascular endothelial growth factor observed in saline-treated transgenic mice compared with wild type, and resulted in a dramatic increase in the expression of the anti-inflammatory interleukin-13. Conclusions. Our results suggest that hMSCs, when intracistemally administered, can exert their paracrine potential, influencing the inflammatory response of the host.