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    • The Anti-Inflammatory Effects of Adipose Tissue Mesenchymal Stem Cell Exosomes in a Mouse Model of Inflammatory Bowel Disease

    Jun Ho Lee,Jan Lotvall,Byong Seung Cho

    International Journal of Molecular Sciences（2023）

    ExoCoBio Inc | Univ Gothenburg

    Cited 2|Views15
    Abstract
    Inflammatory bowel disease (IBD) is a group of chronic, relapsing inflammatory disorders that affect the gastrointestinal tract, with the primary subtypes being ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to evaluate the therapeutic potential of extracellular vesicles released by adipose-tissue-derived mesenchymal stem cells, which we, in this manuscript, call “exosomes” (ASC-EXOs), in a mouse model of IBD. We specifically aimed to determine the effectiveness of different treatment protocols and compare the effects with that of anti-IL-12 p40 monoclonal antibody. The addition of dextran sulfate sodium (DSS) to drinking water induced multiple signs of IBD, including weight loss, soft stool, and bloody feces. ASC-EXOs given by either intraperitoneal (IP) or intravenous (IV) routes resulted in moderate improvement in these signs of IBD. IV ASC-EXOs resulted in significantly reduced body weight loss, improved histopathological scoring, and suppressed the disease activity index (DAI) compared to the IBD control group. Also, a reduction in PCR for pro-inflammatory cytokines was observed. IV ASC treatment resulted in dose-related reduction in IBD signs, including weight loss. An increasing number of injections with ASC-EXOs reduced histopathological scores as well as DAI. Co-administration of ASC-EXOs with anti-IL-12 p40 significantly decreased DAI scores in the ASC-EXO + anti-IL-12 p40 group. In conclusion, ASC-EXOs have potential as a therapeutic agent for IBD, but the route of administration, number of injections, and dosage need to be considered to optimize the effects of ASC-EXO treatment. This study also highlights the potential benefits of combination therapies of ASC-EXOs and anti-IL-12. Our findings pave the way for further studies to unravel the underlying therapeutic mechanisms of ASC-EXOs in IBD treatment.
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    exosome,extracellular vesicles,mesenchymal stem cells,anti-inflammation,inflammatory bowel disease (IBD)
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    【要点】：该论文探讨了脂肪组织来源间充质干细胞外泌体（ASC-EXOs）在治疗小鼠炎症性肠病（IBD）中的抗炎效果，并比较了不同给药方式和联合治疗的疗效。
    

    【方法】：研究通过将脂肪组织来源的间充质干细胞外泌体（ASC-EXOs）通过腹腔注射（IP）和静脉注射（IV）两种方式给予IBD模型小鼠，并设置抗IL-12 p40单抗作为对照组，以评估ASC-EXOs的治疗效果。
    

    【实验】：实验使用的是小鼠炎症性肠病模型，通过在饮用水中添加硫酸葡聚糖钠（DSS）诱导IBD症状。实验结果显示，IV ASC-EXOs组相较于对照组在体重减轻、组织病理学评分和疾病活动指数（DAI）方面均有显著改善，且PCR检测显示炎症因子水平降低。同时，ASC-EXOs与抗IL-12 p40联合使用显著降低了DAI评分。