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5-氨基水杨酸对间充质干细胞治疗溃疡性结肠炎小鼠模型疗效的影响。

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

机构信息

The Suqian Clinical College of Xuzhou Medical University, 120 Su zhi Road, Sucheng District, Suqian 223800, China.

Department of Cell Biology, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, 199 Ren Ai Road, Suzhou Industrial Park, Suzhou 215123, China.

出版信息

Int Immunopharmacol. 2024 Jun 15;134:112255. doi: 10.1016/j.intimp.2024.112255. Epub 2024 May 13.

Abstract

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

摘要

炎症性肠病(IBD)的特征是胃肠道持续的免疫介导的炎症。先前的实验研究表明,间充质干细胞(MSC)为基础的治疗在治疗 IBD 方面具有令人鼓舞的结果。然而,作为 IBD 患者的主要药物,关于 5-氨基水杨酸(5-ASA)和 MSC 之间潜在相互作用的信息有限。在本研究中,我们采用葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠模型,研究 MSC 和 5-ASA 联合使用对 UC 发展的影响。对小鼠进行体重测量、DAI 评分、钙卫蛋白表达评估以及结肠收集进行组织学检查。结果表明,5-ASA 和 MSC 均对 UC 治疗有效。然而,值得注意的是,5-ASA 起效更快,而 MSC 则表现出更有利且持久的治疗效果。此外,5-ASA 和 MSC 联合治疗的疗效不如 MSC 单独治疗组。此外,我们在体外进行的研究表明,5-ASA 可以促进 MSC 迁移,但也可以抑制 MSC 增殖,诱导细胞凋亡,过度表达炎症因子(IL-2、IL-12P70 和 TNF-α),并降低 PD-L1 和 PD-L2 的表达。此外,由于 5-ASA 的诱导,在结肠内观察到 MSC 活力显著下降。这些发现共同表明,5-ASA 的使用有可能干扰 MSC 移植治疗 IBD 的治疗效果。

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