Human Fallopian Tube – Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System,Stem Cell Reviews and Reports

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Human Fallopian Tube – Derived Mesenchymal Stem Cells Inhibit Experimental Autoimmune Encephalomyelitis by Suppressing Th1/Th17 Activation and Migration to Central Nervous System
Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-08-28 , DOI: 10.1007/s12015-021-10226-7
Carla Longo de Freitas _{1,

2} , Carolina Manganeli Polonio _{1,

2} , Wesley Nogueira Brandão _{1,

2} , Cristiano Rossato _{1,

2} , Nágela Ghabdan Zanluqui _{1,

2,

3} , Lilian Gomes de Oliveira _{1,

2} , Marília Garcia de Oliveira _{1,

2} , Lucila Pires Evangelista _{2,

4} , Silvio Halpern _{2,

5} , Mariangela Maluf _{2,

6} , Carlos Eduardo Czresnia _{2,

4} , Paulo Perin _{2,

6} , Danilo Candido de Almeida _{2,

7} , Jean Pierre Schatzmman Peron _{1,

2,

3}

Affiliation

Mesenchymal stem cells comprise a natural reservoir of undifferentiated cells within adult tissues. Given their self-renewal, multipotency, regenerative potential and immunomodulatory properties, MSCs have been reported as a promising cell therapy for the treatment of different diseases, including neurodegenerative and autoimmune diseases. In this study, we investigated the immunomodulatory properties of human tubal mesenchymal stem cells (htMSCs) using the EAE model. htMSCs were able to suppress dendritic cells activation downregulating antigen presentation-related molecules, such as MHCII, CD80 and CD86, while impairing IFN-γ and IL-17 and increasing IL-10 and IL-4 secretion. It further correlated with milder disease scores when compared to the control group due to fewer leukocytes infiltrating the CNS, specially Th1 and Th17 lymphocytes, associated with increased IL-10 secreting Tr1 cells. Conversely, microglia were less activated and infiltrating mononuclear cells secreted higher levels of IL-4 and IL-10 and expressed reduced chemokine receptors as CCR4, CCR6 and CCR8. qPCR of the spinal cords revealed upregulation of indoleamine-2,3-dioxygenase (IDO) and brain derived neurotrophic factor (BDNF). Taken together, here evidenced the potential of htMSCs as an alternative for the treatment of inflammatory, autoimmune or neurodegenerative diseases.

Graphical abstract

中文翻译：

人类输卵管 - 衍生间充质干细胞通过抑制 Th1/Th17 激活和迁移到中枢神经系统来抑制实验性自身免疫性脑脊髓炎

间充质干细胞包含成人组织内未分化细胞的天然储存库。鉴于其自我更新、多能性、再生潜力和免疫调节特性，MSCs 已被报道为治疗不同疾病（包括神经退行性疾病和自身免疫性疾病）的有前途的细胞疗法。在这项研究中，我们使用 EAE 模型研究了人输卵管间充质干细胞 (htMSCs) 的免疫调节特性。htMSCs 能够抑制树突状细胞活化，下调抗原呈递相关分子，如 MHCII、CD80 和 CD86，同时削弱 IFN-γ 和 IL-17 并增加 IL-10 和 IL-4 分泌。与对照组相比，由于浸润中枢神经系统的白细胞较少，特别是 Th1 和 Th17 淋巴细胞，它进一步与较轻的疾病评分相关，与分泌 IL-10 的 Tr1 细胞增加有关。相反，小胶质细胞的活化较少，浸润的单核细胞分泌较高水平的 IL-4 和 IL-10，并表达减少的趋化因子受体，如 CCR4、CCR6 和 CCR8。脊髓的 qPCR 显示吲哚胺-2,3-双加氧酶 (IDO) 和脑源性神经营养因子 (BDNF) 的上调。总之，这里证明了 htMSCs 作为治疗炎症、自身免疫或神经退行性疾病的替代品的潜力。3-双加氧酶 (IDO) 和脑源性神经营养因子 (BDNF)。总之，这里证明了 htMSCs 作为治疗炎症、自身免疫或神经退行性疾病的替代品的潜力。3-双加氧酶 (IDO) 和脑源性神经营养因子 (BDNF)。总之，这里证明了 htMSCs 作为治疗炎症、自身免疫或神经退行性疾病的替代品的潜力。

图形概要

更新日期：2021-08-29

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