Department of Gastroenterology, the First Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
Department of Gastroenterology, the Sixth Medical Center, General Hospital of the Chinese People's Liberation Army, No. 6, Fu Cheng Road, Hai Dian District, Beijing 100048, China.
Cell Immunol. 2022 Oct;380:104573. doi: 10.1016/j.cellimm.2022.104573. Epub 2022 Jul 5.
Considering the possible interaction between mesenchymal stem cells (MSCs) and PI3Kγ-associated drugs, we evaluated the efficacy and action mechanism of MSCs in the treatment of colitis in PI3Kγ-/- mice. Trinitro-benzene-sulfonic acid enema was used to create a colitis model, and MSCs were transplanted through the caudal vein to treat colitis in wild-type and PI3Kγ-/- mice. We sequenced microbial 16S rRNA genes in the colonic mucosa of PI3Kγ-/- and wild-type mice and quantified colonic IgA, IL-2, IL-10, IL-17A, occludin, and serum IgA. MSC transplantation led to a more serious reduction in the weight of trinitro-benzene-sulfonic acid-administered PI3Kγ-/- mice than that in wild-type mice. The disease activity index, pathological scoring, number of taxa in the colon, Berger-Parker index, I-index, proportion of Proteobacteria, and IgA level in the blood were higher in PI3Kγ-/- mice than in wild-type mice after MSC transplantation. The occludin and IL-10 levels in the colon tissues decreased before and after MSC transplantation in PI3Kγ-/- mice, whereas they were increased in wild-type mice The IL-17 level decreased in both wild-type and PI3Kγ-/- mice, with knockout mice showing a greater decrease. Therefore, MSC transplantation in PI3Kγ-/- mice led to increased numbers of exogenous pathogenic microorganisms and enhanced colitis that was difficult to relieve.
考虑到间充质干细胞（MSCs）与 PI3Kγ 相关药物之间可能存在的相互作用，我们评估了 MSCs 在治疗 PI3Kγ-/- 小鼠结肠炎中的疗效和作用机制。使用三硝基苯磺酸灌肠法建立结肠炎模型，通过尾静脉移植 MSCs 治疗野生型和 PI3Kγ-/- 小鼠结肠炎。我们对 PI3Kγ-/- 和野生型小鼠结肠黏膜的微生物 16S rRNA 基因进行测序，并定量检测结肠 IgA、IL-2、IL-10、IL-17A、occludin 和血清 IgA。与野生型小鼠相比，MSCs 移植后，三硝基苯磺酸处理的 PI3Kγ-/- 小鼠体重下降更为严重。与野生型小鼠相比，PI3Kγ-/- 小鼠移植 MSC 后疾病活动指数、病理评分、结肠菌群数量、Berger-Parker 指数、I 指数、变形菌比例和血清 IgA 水平更高。PI3Kγ-/- 小鼠 MSC 移植前后结肠组织中 occludin 和 IL-10 水平降低，而野生型小鼠则升高。IL-17 水平在野生型和 PI3Kγ-/- 小鼠中均降低，敲除小鼠降低更明显。因此，PI3Kγ-/- 小鼠 MSC 移植导致外源性致病微生物数量增加，并且结肠炎加重，难以缓解。
