间充质基质细胞（MSC）在炎症性肠病中的治疗功效尚不完全清楚且不一致。已提出用炎症细胞因子引发以使间充质干细胞适应炎症环境，使其做好抵抗炎症的准备，但可能对间充质干细胞产生不良影响，例如免疫原性增加。在这项研究中，我们假设用发炎的肠道组织启动 MSC 将更有效地增强其对肠道炎症的治疗效果。用来自实验诱导结肠炎的小鼠的结肠组织匀浆或组合来启动犬脂肪源性 MSC (cADSC) 的能力分析了肿瘤坏死因子-α 和干扰素-γ 抑制 T 细胞增殖的作用，以及它们自身的凋亡、增殖、细胞表面标志物表达和转录组。此外，用引发的 cADSC 治疗结肠炎小鼠，以评估结肠炎的严重程度和免疫细胞特征。用细胞因子引发的 cADSC 会诱导细胞凋亡、细胞增殖减少和主要组织相容性复合物 II 基因表达，但这些不良反应轻微或不存在结肠炎组织启动。用结肠炎组织引发的 cADSC 通过诱导 M2 巨噬细胞和 T 调节细胞以及抑制 T 辅助细胞 (Th)1/Th17 细胞反应，降低了结肠炎的严重程度，其效果与细胞因子引发的细胞相当。我们的结果强调了通过适当的微环境激活 MSC 以最大限度地提高其治疗效果的重要性。版权所有 © 2024 Yasumura、Teshima、Nagashima、Michishita、Taira、Suzuki 和 Matsumoto。

The therapeutic efficacy of mesenchymal stromal cells (MSCs) in inflammatory bowel disease is not completely known and is not consistent. Priming with inflammatory cytokines has been proposed to adapt MSCs to an inflammatory environment to have them ready to counteract it, but may have undesirable effects on MSCs, such as increased immunogenicity. In this study, we hypothesized that priming MSCs with inflamed intestinal tissue would more effectively enhance their therapeutic effect on intestinal inflammation.The capacity of canine adipose-derived MSCs (cADSCs) primed with colon tissue homogenates from mice with experimentally induced colitis or a combination of tumor necrosis factor-α and interferon-γ to inhibit T-cell proliferation was analyzed, along with their own apoptosis, proliferation, cell surface marker expression, and transcriptome. In addition, colitis mice were treated with the primed cADSCs to assess colitis severity and immune cell profile.Priming with cytokines induced apoptosis, decreased cell proliferation, and major histocompatibility complex-II gene expression in cADSCs, but these adverse effects were mild or absent with colitis-tissue priming. cADSCs primed with colitis tissue reduced the severity of colitis via the induction of M2 macrophages and T-regulatory cells and suppression of T-helper (Th)1/Th17-cell responses, and their effects were comparable to those of cytokine-primed cells.Our results emphasize the importance of the activation of MSCs by the appropriate microenvironment to maximize their therapeutic effect.Copyright © 2024 Yasumura, Teshima, Nagashima, Michishita, Taira, Suzuki and Matsumoto.