Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease
Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease
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DOI：
10.1016/j.jneuroim.2009.09.003
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发表时间：
2009-11-30
影响因子：
3.3
通讯作者：
Tay, Samuel Sam Wah
中科院分区：
文献类型：
--
作者：
Chao, Yin Xia;He, Bei Ping;Tay, Samuel Sam Wah
在mptp诱导的小鼠模型中，研究了移植间充质干细胞（MSCs）在帕金森病治疗中的免疫调节作用。MPTP治疗大鼠多巴胺能神经元明显减少，致密黑质（SNc）中claudin 1、claudin 5和occludin的表达降低，血脑屏障（BBB）功能受损。本研究进一步发现，mptp处理小鼠SNc中检测到MBL浸润入脑并与小胶质细胞结合，提示血脑屏障受损和MBL浸润可能参与了mptp诱导PD的发病机制。此外，MPTP处理还增加了肝组织中甘露糖结合凝集素（MBLs）的表达。将MSCs静脉移植到mptp处理的小鼠体内，可以恢复血脑屏障的完整性，抑制MBL在SNc的浸润和肝脏中MBL的表达，抑制小胶质细胞的激活，防止多巴胺能神经元的死亡。未观察到移植的间充质干细胞分化为多巴胺能神经元，而间充质干细胞迁移到SNc并释放tgf - β 1。因此，静脉移植保护多巴胺能神经元免受MPTP毒性的间充质干细胞可能参与任何或这些机制的组合：修复血脑屏障，减少脑内MBL，抑制小胶质细胞毒性，直接保护多巴胺能神经元。(C) 2009 Elsevier B.V.版权所有
Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta 1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons. (C) 2009 Elsevier B.V. All rights reserved.