Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis.
Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis.
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间充质干细胞衍生的外泌体对实验性自身免疫性葡萄膜炎的影响
DOI：
10.1038/s41598-017-04559-y
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发表时间：
2017-06-28
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
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作者：
Bai L;Shao H;Wang H;Zhang Z;Su C;Dong L;Yu B;Chen X;Li X;Zhang X
我们之前证明间充质干细胞（MSC）可以改善大鼠实验性自身免疫性葡萄膜视网膜炎（EAU）。最近，MSC 衍生的外泌体（MSC-Exo）被认为携带 MSC 的功能。在这项研究中，我们测试了局部施用人 MSC-Exo 对同一物种中已建立的 EAU 的影响。通过光感受器间视黄醇结合蛋白 1177-1191 肽免疫诱导的 EAU 大鼠，从疾病发作时开始连续 7 天眼周注射增加剂量的 MSC-Exo 进行治疗。分别通过趋化试验和淋巴细胞增殖试验检查 MSC-Exo 对免疫细胞迁移和应答 T 细胞增殖的体外影响。我们发现，MSC-Exo 通过减少眼睛中 T 细胞亚群和其他炎症细胞的浸润，大大降低了作为其母细胞的持续 EAU 的强度。此外，CCL2和CCL21对炎症细胞的化学吸引作用被MSC-Exo抑制。然而，没有观察到 MSC-Exo 对 IRBP 特异性 T 细胞增殖的抑制作用。这些结果表明 MSC-Exo 通过抑制炎症细胞的迁移有效改善 EAU，表明 MSC-Exo 是治疗葡萄膜炎的潜在新疗法。
We previously demonstrated that mesenchymal stem cells (MSCs) ameliorated experimental autoimmune uveoretinitis (EAU) in rats. Recently, MSC-derived exosomes (MSC-Exo) were thought to carry functions of MSCs. In this study, we tested the effect of local administration of human MSC-Exo on established EAU in the same species. Rats with EAU induced by immunization with interphotoreceptor retinol-binding protein 1177–1191 peptide were treated by periocular injections of increasing doses of MSC-Exo starting at the disease onset for 7 consecutive days. Thein vitroeffects of MSC-Exo on immune cell migration and responder T cell proliferation were examined by chemotactic assays and lymphocyte proliferation assays, respectively. We found that MSC-Exo greatly reduced the intensity of ongoing EAU as their parent cells by reducing the infiltration of T cell subsets, and other inflammatory cells, in the eyes. Furthermore, the chemoattractive effects of CCL2 and CCL21 on inflammatory cells were inhibited by MSC-Exo. However, no inhibitory effect of MSC-Exo on IRBP-specific T cell proliferation was observed. These results suggest that MSC-Exo effectively ameliorate EAU by inhibiting the migration of inflammatory cells, indicating a potential novel therapy of MSC-Exo for uveitis.