患有炎症性肠病（IBD）的患者发展为结肠相关性结直肠癌（CAC）的风险较高，预后不良。IBD的病因尚未明确，但涉及环境因素、遗传易感性、微生物群失衡（菌群失调）和粘膜免疫缺陷。动物和人体研究表明，间充质基质细胞（MSCs）注射对减轻肠道炎症表现出良好的疗效。然而，它们对CAC的肿瘤生长的影响和恢复肠道菌群失调的能力尚不明确。通过在C57BL / 6J小鼠的AOM / DSS CAC模型中评估体外扩增的人肠道MSCs（iMSCs）对体内肿瘤生长的结果，并通过流式细胞术分析血液、腹膜淋巴结（MLNs）和结肠组织的先天和适应性免疫应答。通过16S rRNA引物测序评估肠道微生物组成。iMSCs显著抑制结肠炎和肠道肿瘤发展，减少IL-6和COX-2的表达，降低IL-6 / STAT3和PI3K / Akt信号传导。iMSCs减少了结肠免疫细胞浸润，并在一定程度上恢复了肠道单核细胞的归巢和分化。iMSCs的给药增加MLNs中Tregs和IFN-γ + CD8 + T细胞的数量，同时降低了IL-4 + Th2应答。它还改善了CAC小鼠的肠道菌群失衡，增加了多样性和芽孢杆菌科/拟杆菌科比例，同时减少了与炎症相关的Alistipes和Turicibacter属菌。iMSCs的给药对CAC具有保护作用，改善结肠炎症，部分逆转肠道菌群失衡，支持使用MSCs治疗IBD。版权©2023年。由Elsevier Ltd出版。

Patients with Inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated colorectal cancer (CAC) with poor prognosis. IBD etiology remains undefined but involves environmental factors, genetic predisposition, microbiota imbalance (dysbiosis) and mucosal immune defects. Mesenchymal stromal cells (MSCs) injections have shown good efficacy in reducing intestinal inflammation in animal and human studies. However, their effect on tumor growth in CAC and their capacity to restore gut dysbiosis is not clear.The outcome of systemic administrations of in vitro expanded human intestinal MSCs (iMSCs) on tumor growth in vivo was evaluated using the AOM/DSS model of CAC in C57BL/6J mice. Innate and adaptive immune responses in blood, mesenteric lymph nodes (MLNs) and colonic tissue were analyzed by flow cytometry. Intestinal microbiota composition was evaluated by 16S rRNA Amplicon Sequencing.iMSCs significantly inhibited colitis and intestinal tumor development, reducing IL-6 and COX-2 expression, and IL-6/STAT3 and PI3K/Akt signaling. iMSCs decreased colonic immune cell infiltration, and partly restored intestinal monocyte homing and differentiation. iMSC administration increased the numbers of Tregs and IFN-γ+CD8+ T cells in the MLNs while decreasing the IL-4+Th2 response. It also ameliorated intestinal dysbiosis in CAC mice, increasing diversity and Bacillota/Bacteroidota ratio, as well as Akkermansia abundance, while reducing Alistipes and Turicibacter, genera associated with inflammation.Administration of iMSCs protects against CAC, ameliorating colitis and partially reverting intestinal dysbiosis, supporting the use of MSCs for the treatment of IBD.Copyright © 2023. Published by Elsevier Ltd.