Fei Gao1, Dandan Cui1, Dongmei Zuo1, Zhexing Shou2, Jia Yang1, Ting Yu1, Yujin Liu1, Si Chu1, Feng Zhu1, Chunzhu Wei1. 1. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 36747601@qq.com.
Abstract
OBJECTIVES: 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). RESULTS: 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 × 106 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. CONCLUSIONS: 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.
OBJECTIVES: 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). RESULTS: 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 × 106 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. CONCLUSIONS: 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.
Authors: Elie El Agha; Rafael Kramann; Rebekka K Schneider; Xiaokun Li; Werner Seeger; Benjamin D Humphreys; Saverio Bellusci Journal: Cell Stem Cell Date: 2017-08-03 Impact factor: 24.633
Authors: Floris Dammeijer; Mandy van Gulijk; Evalyn E Mulder; Melanie Lukkes; Larissa Klaase; Thierry van den Bosch; Menno van Nimwegen; Sai Ping Lau; Kitty Latupeirissa; Sjoerd Schetters; Yvette van Kooyk; Louis Boon; Antien Moyaart; Yvonne M Mueller; Peter D Katsikis; Alexander M Eggermont; Heleen Vroman; Ralph Stadhouders; Rudi W Hendriks; Jan von der Thüsen; Dirk J Grünhagen; Cornelis Verhoef; Thorbald van Hall; Joachim G Aerts Journal: Cancer Cell Date: 2020-10-01 Impact factor: 31.743