Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis.
Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis.
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DOI：
10.1002/glia.20841
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发表时间：
2009-08-15
期刊：
影响因子：
6.2
通讯作者：
Miller, Robert H.
中科院分区：
文献类型：
--
作者：
Bai, Lianhua;Lennon, Donald P.;Eaton, Valerie;Maier, Kari;Caplan, Arnold I.;Miller, Stephen D.;Miller, Robert H.
基于细胞的治疗是促进髓鞘修复的有吸引力的方法。最近的研究表明，用小鼠间充质干细胞(MSCs)治疗EAE可以减轻小鼠的疾病负担。在这里，我们证明了人骨髓间充质干细胞(BM-hMSCs)促进了慢性和复发-缓解小鼠EAE模型的功能恢复，追踪了它们向受损中枢的迁移，并分析了它们调节疾病进展和宿主免疫反应的能力。注射BM-hMSCs后，BM-hMSCs聚集在中枢神经系统，损伤程度减轻，病变区少突胶质细胞增多。皮损中少突胶质细胞的增加可能反映了BM-hMSC诱导的神经命运决定的改变，因为处理动物的神经球比未处理的神经球产生更多的少突胶质细胞和更少的星形胶质细胞。BM-hMSCs对宿主免疫反应也有影响。炎性T细胞，包括产生干扰素-γ的Th1细胞和产生IL-17的Th17炎性细胞及其相关细胞因子减少，同时产生IL-4的Th2细胞和抗炎细胞因子增加。总之，这些数据表明BM-hMSCs是一种可行的治疗方法。
Cell based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with EAE treated with mouse mesenchymal stem cells (MSCs). Here we demonstrated human bone marrow derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM-hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM-hMSC induced changes in neural fate determination since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than non-treated neurospheres. Host immune responses were also influenced by BM-hMSCs. Inflammatory T-cells including interferon gamma (IFN-γ) producing Th1 cells and IL-17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL-4 producing Th2 cells and anti-inflammatory cytokines. Together these data suggest the BM-hMSCs represent a viable option for therapeutic approaches.
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影响因子：
82.9
作者：
Linker, RA;Mäurer, M;Gold, R
通讯作者：
Gold, R
影响因子：
3.7
作者：
Aharonowiz M;Einstein O;Fainstein N;Lassmann H;Reubinoff B;Ben-Hur T
通讯作者：
Ben-Hur T
影响因子：
5.3
作者：
Ankeny, DP;McTigue, DM;Jakeman, LB
通讯作者：
Jakeman, LB
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF
影响因子：
4
作者：
Caplan, Arnold I.;Dennis, James E.
通讯作者：
Dennis, James E.