Labolatory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine and Research institute for Veterinary Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon-si, Gyeonggi-do, 16419, Republic of Korea.
Sci Rep. 2020 Feb 7;10(1):2115. doi: 10.1038/s41598-020-58909-4.
The inflammatory bowel diseases (IBD) are characterized by relapsing inflammation and immune activation diseases of the gastrointestinal tract. Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential. In this study, we investigated whether the Extracellular vesicles (EVs) obtained by stimulating inflammatory cytokine on canine adipose mesenchymal stem cells (cASC) improved anti-inflammatory and/or immunosuppressive potential of EVs, and/or their ability to alleviate inflammation in colitis. We also explored the correlation between immune cells and the inflammatory repressive effect of primed EVs. Pro-inflammatory cytokines such as TNF-α and IFN-γ increased immunosuppressive protein such as HGF, TSG-6, PGE2 and TGF-β in EVs. Moreover, the anti-inflammatory effect of EVs was improved through pretreatment with inflammatory cytokines. Importantly, EVs obtained from primed stem cells effectively induced macrophage polarization toward an anti-inflammatory M2 phenotype and suppressed activated immunity by enhancing regulatory T cells in inflamed colon in mice. Our results provide a new and effective therapy for the EVs obtained from ASC stimulated with TNF-α and IFN-γ against not only IBD, but also immune-mediated disease.
炎症性肠病（IBD）的特征是胃肠道反复发作的炎症和免疫激活疾病。细胞外囊泡（extracellular vesicles，EVs）具有与干细胞相似的生物学活性，已被用于实验治疗葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的小鼠结肠炎模型，具有免疫抑制潜力。在本研究中，我们研究了犬脂肪间充质干细胞（canine adipose mesenchymal stem cells，cASC）经炎性细胞因子刺激获得的细胞外囊泡（extracellular vesicles，EVs）是否能改善 EVs 的抗炎和/或免疫抑制潜力，以及它们减轻结肠炎炎症的能力。我们还探讨了免疫细胞与预刺激 EVs 的抗炎抑制作用之间的相关性。促炎细胞因子如 TNF-α和 IFN-γ增加了 EVs 中的免疫抑制蛋白，如 HGF、TSG-6、PGE2 和 TGF-β。此外，通过用炎性细胞因子预处理，EVs 的抗炎作用得到改善。重要的是，来自预刺激干细胞的 EVs 有效地诱导巨噬细胞向抗炎 M2 表型极化，并通过增强炎症结肠中的调节性 T 细胞来抑制激活的免疫。我们的研究结果为 ASC 经 TNF-α和 IFN-γ刺激获得的 EVs 提供了一种新的有效治疗方法，不仅针对 IBD，还针对免疫介导的疾病。
