Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells Alleviate Dextran Sulfate Sodium-Induced Colitis by Increasing Regulatory T Cells in Mice.
Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells Alleviate Dextran Sulfate Sodium-Induced Colitis by Increasing Regulatory T Cells in Mice.
复制标题
人脐带血源性间充质干细胞通过增加小鼠调节性 T 细胞缓解硫酸葡聚糖钠诱导的结肠炎
DOI：
10.3389/fcell.2020.604021
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Li Y;Ma K;Zhang L;Xu H;Zhang N
炎症性肠病（Inflammatory bowel disease，IBD）是一种自身免疫性疾病，主要临床表现为反复发作的腹痛和腹泻。已有研究报道，间充质干细胞（MSCs）可以通过调节免疫细胞的功能来减轻炎症。但目前对间充质干细胞与适应性免疫细胞之间相互作用的研究，特别是在IBD模型中的研究还不够充分。因此，本研究的目的是评价人脐带血间充质干细胞（hUCB-MSCs）对大鼠IBD模型的治疗作用，并阐明hUCB-MSCs的治疗机制。用右旋糖酐硫酸钠（DSS）诱导啮齿动物结肠炎。用腹膜内输注hUCB-MSC治疗患有结肠炎的小鼠，并评估死亡率和多种疾病症状，包括体重减轻、腹泻和血便。还测定了组织病理学严重程度和调节性T细胞（Treg）的产生水平。用hUCB-MSC治疗改善了小鼠中急性和慢性结肠炎的临床和组织病理学严重程度。此外，T细胞浸润到发炎的结肠中显著减少（p = 0.0175），并且Foxp 3+细胞在hUCB-MSC组中显著高于DSS组。我们的研究结果表明，hUCB-MSCs能够通过在小鼠IBD模型中添加Foxp 3 + T细胞来减轻炎症。因此，这些发现表明hUCB-MSC有机会应用于IBD患者。
Inflammatory bowel disease (IBD), which main clinical manifestations include abdominal pain and diarrhea occurring repeatedly, is a kind of autoimmune disease. It has been reported in preceding studies that mesenchymal stem cells (MSCs) can reduce inflammation by regulating the function of immune cells. But studies about the interaction between MSCs and adaptive immune cells, especially in IBD models, are insufficient. Therefore, the objective of this research was to estimate the therapeutic effects of MSCs from human umbilical cord blood (hUCB-MSCs) in an IBD model of rodent and to clarify the therapeutic mechanisms of hUCB-MSCs. Dextran sulfate sodium (DSS) was used to induce colitis in rodent. Mice with colitis were treated with intraperitoneal infusions of hUCB-MSCs and evaluated for mortality and diverse disease symptoms containing weight reduction, diarrhea, and bloody stools. The levels of histopathologic severity and generation of regulatory T cells (Treg) were also determined. Treatment with hUCB-MSCs ameliorated the clinical and histopathologic severity of acute and chronic colitis in mice. Furthermore, T cell infiltration into the inflamed colon was significantly decreased (p = 0.0175), and Foxp3+ cells were substantially higher in the hUCB-MSC group than that of the DSS group. Our results suggest that hUCB-MSCs are able to alleviate inflammation via adding Foxp3+ Tregs in an IBD model of mouse. As a result, these findings suggest the opportunity of hUCB-MSC being applied to patients with IBD.