Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
J Neuroimmunol. 2009 Nov 30;216(1-2):39-50. doi: 10.1016/j.jneuroim.2009.09.003. Epub 2009 Oct 9.
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-beta1 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.
研究了移植间充质干细胞（MSCs）在治疗帕金森病中的免疫调节作用，该研究使用了 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠模型。MPTP 处理诱导多巴胺能神经元显著丧失，致密部黑质（SNc）中 Claudin 1、Claudin 5 和 Occludin 的表达降低，血脑屏障（BBB）的功能受损。我们的研究进一步发现，MPTP 处理小鼠的 SNc 中检测到 MBL 渗透到大脑并与小胶质细胞结合，这表明 BBB 破坏和 MBL 渗透可能参与 MPTP 诱导的 PD 的发病机制。此外，MPTP 处理还增加了肝脏组织中甘露糖结合凝集素（MBLs）的表达。将 MSCs 静脉移植到 MPTP 处理的小鼠中，导致 BBB 完整性恢复，SNc 处 MBL 渗透减少，肝脏中 MBL 表达减少，小胶质细胞激活抑制和多巴胺能神经元死亡预防。未观察到移植的 MSCs 分化为多巴胺能神经元，而 MSCs 迁移到 SNc 并在那里释放 TGF-β1。因此，静脉内移植 MSCs 可能通过以下一种或多种机制保护多巴胺能神经元免受 MPTP 毒性：修复 BBB、减少脑内 MBL、抑制小胶质细胞细胞毒性和直接保护多巴胺能神经元。
