Accelerated and enhanced effect of CCR5-transduced bone marrow neural stem cells on autoimmune encephalomyelitis.
Accelerated and enhanced effect of CCR5-transduced bone marrow neural stem cells on autoimmune encephalomyelitis.
复制标题
CCR5转导的骨髓神经干细胞对自身免疫性脑脊髓炎的加速和增强作用
DOI：
10.1007/s00401-012-0989-1
复制
发表时间：
2012-10
影响因子：
12.7
通讯作者：
Zhang GX
中科院分区：
文献类型：
--
作者：
Yang J;Yan Y;Ma CG;Kang T;Zhang N;Gran B;Xu H;Li K;Ciric B;Zangaladze A;Curtis M;Rostami A;Zhang GX
神经干细胞（NSCs）对多发性硬化（MS）动物模型实验性自身免疫性脑脊髓炎（EAE）的抑制作用已有报道。然而，神经干细胞向炎症部位的迁移相对缓慢，临床获益也相当有限。神经干细胞上特定趋化因子受体的缺乏或低表达可能是神经干细胞迁移缓慢的重要因素。为了增强神经干细胞的治疗效果，在本研究中，我们用CCR 5转导骨髓（BM）来源的神经干细胞，CCL 3，CCL 4和CCL 5的受体，这些趋化因子在MS/EAE的CNS炎症灶中大量产生。静脉注射后，CCR 5-NSC以更大数量迅速到达EAE病灶，并且比用作对照的GFP-NSC更有效地抑制CNS炎性浸润、髓鞘损伤和临床EAE。与PBS-或GFP-NSC-处理的小鼠相比，CCR 5-NSC-处理的小鼠还表现出增强的髓鞘再生和神经元/少突胶质细胞再增殖。我们推断，CCR 5转导的神经干细胞对EAE的增强作用的关键机制是趋化因子受体转导的神经干细胞早期迁移到炎症灶中。在炎症的早期阶段的这种迁移使得NSC能够发挥更有效的免疫调节作用，通过为髓鞘再生细胞创造较不敌对的环境来降低早期髓鞘/神经元损伤的程度，并且可能参与髓鞘再生/神经再生过程。BM衍生的转导的NSC的这些特征，结合它们的容易获得性（受试者自身的BM）和自体特性，可以为快速和高效的MS治疗的创新方法奠定基础。
The suppressive effect of neural stem cells (NSCs) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), has been reported. However, the migration of NSCs to inflammatory sites was relatively slow as was the onset of rather limited clinical benefit. Lack of, or low expression of particular chemokine receptors on NSCs could be an important factor underlying the slow migration of NSCs. To enhance the therapeutic effect of NSCs, in the present study we transduced bone marrow (BM)-derived NSCs with CCR5, a receptor for CCL3, CCL4, and CCL5, chemokines that are abundantly produced in CNS-inflamed foci of MS/EAE. After i.v. injection, CCR5-NSCs rapidly reached EAE foci in larger numbers, and more effectively suppressed CNS inflammatory infiltration, myelin damage, and clinical EAE than GFP-NSCs used as controls. CCR5-NSC-treated mice also exhibited augmented remyelination and neuron/oligodendrocyte repopulation compared to PBS- or GFP-NSC-treated mice. We inferred that the critical mechanism underlying enhanced effect of CCR5-transduced NSCs on EAE is the early migration of chemokine receptor-transduced NSCs into the inflamed foci. Such migration at an earlier stage of inflammation enables NSCs to exert more effective immunomodulation, to reduce the extent of early myelin/neuron damage by creating a less hostile environment for remyelinating cells, and possibly to participate in the remyelination/neural repopulation process. These features of BM-derived transduced NSCs, combined with their easy availability (the subject’s own BM) and autologous properties, may lay the groundwork for an innovative approach to rapid and highly effective MS therapy.
登录
查看更多内容
影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
--
作者：
Man S;Ubogu EE;Williams KA;Tucky B;Callahan MK;Ransohoff RM
通讯作者：
Ransohoff RM
影响因子：
3.6
作者：
Guan, Yangtai;Jiang, Zhilong;Zhang, Guang-Xian
通讯作者：
Zhang, Guang-Xian
DOI：
10.1196/annals.1345.007
发表时间：
2005-01-01
期刊：
COOLEY'S ANEMIA EIGHTH SYMPOSIUM
影响因子：
--
作者：
Bank, A;Dorazio, R;Leboulch, P
通讯作者：
Leboulch, P
影响因子：
4.4
作者：
Doering, Axinia;Wild, Martin;Engelhardt, Britta
通讯作者：
Engelhardt, Britta