Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Biotechnol Lett. 2022 Nov;44(11):1263-1275. doi: 10.1007/s10529-022-03307-1. Epub 2022 Oct 20.
Bone marrow-derived mesenchymal stem cells (BMSCs) show promise in treating inflammatory bowel disease. We tested if BMSCs improve Trinitro-benzene-sulfonic acid (TNBS)-induced colitis by inducing Treg differentiation by modulating programmed cell death 1 ligand 1(PD-L1).
BMSCs were isolated and transfected with PD-L1 siRNA. Sprague-Dawley rats were randomly divided into 4 groups: normal, model, BMSC control, and PD-L1 siRNA BMSC. Colitis was induced by TNBS, except in the normal group. On d4, the BMSC control and PD-L1 siRNA BMSC groups were intravenously injected with BMSCs at a dose of 5 × 10 cells in phosphate-buffered saline (PBS; volume matched). BMSCs were later verified to have reached the colon tissue. BMSC control showed significantly better clinical symptoms and reduced histopathological colitis severity; PD-L1 siRNA BMSC group showed no difference. PD-L1 siRNA reduced: spleen and mesenteric lymph node Tregs, PD-L1, interleukin-10 (IL10), phosphate and tension homology deleted on chromosome ten (PTEN); colon p-Akt and p-mTOR were increased.
We found that BMSCs can induce Treg differentiation by inhibiting the Akt/mTOR pathway via PD-L1; this significantly improved symptoms and pathology in our ulcerative colitis rat models.
骨髓间充质干细胞（BMSCs）在治疗炎症性肠病方面显示出巨大潜力。我们通过调节程序性死亡配体 1（PD-L1）来诱导 Treg 分化，检测 BMSCs 是否可以改善三硝基苯磺酸（TNBS）诱导的结肠炎。
分离并转染 PD-L1 siRNA 的 BMSCs。Sprague-Dawley 大鼠随机分为 4 组：正常组、模型组、BMSC 对照组和 PD-L1 siRNA BMSC 组。除正常组外，其余各组均用 TNBS 诱导结肠炎。在第 4 天，BMSC 对照组和 PD-L1 siRNA BMSC 组以 5×10 个细胞磷酸盐缓冲盐水（PBS；体积匹配）的剂量静脉注射 BMSC。随后证实 BMSC 已到达结肠组织。BMSC 对照组的临床症状明显改善，组织病理学结肠炎严重程度降低；而 PD-L1 siRNA BMSC 组无差异。PD-L1 siRNA 减少了：脾和肠系膜淋巴结 Tregs、PD-L1、白细胞介素 10（IL10）、磷酸和张力同源缺失的染色体 10（PTEN）；结肠 p-Akt 和 p-mTOR 增加。
我们发现 BMSCs 可以通过 PD-L1 抑制 Akt/mTOR 通路诱导 Treg 分化；这显著改善了我们溃疡性结肠炎大鼠模型的症状和病理。
