Umbilical Cord-Derived Mesenchymal Stem Cells Attenuate S100-Induced Autoimmune Hepatitis via Modulating Th1 and Th17 Cell Responses in Mice.

IF 3.8 3区 医学 Q2 CELL & TISSUE ENGINEERING
Stem Cells International Pub Date : 2023-10-17 eCollection Date: 2023-01-01 DOI:10.1155/2023/9992207
Xiaofeng Wei, Xinhong Cheng, Yang Luo, Xun Li
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Abstract

Currently, the first-line treatment for autoimmune hepatitis (AIH) is still the combination of glucocorticoids or immunosuppressants. However, hormone and immunosuppressive therapy can cause serious side effects, such as Cushing syndrome and bone marrow suppression. Previous studies reported on the applicability and safety of mesenchymal stem cells (MSCs) to ameliorate liver inflammation and fibrosis. However, the characteristics of MSCs sources directly contribute to the different conclusions on the mechanisms underlying MSC-mediated immunoregulation. Bone marrow-derived MSCs can exert an immunosuppression effect to ameliorate the S100-induced AIH model by inhibiting several proinflammatory cytokines and upregulating of PD-L1 in liver tissue. It is not clear whether human umbilical cord-derived MSCs (hUC-MSCs) could directly inhibit liver inflammation and ultimately alleviate the dysfunction of hepatocytes in the AIH model. First, hUC-MSCs were extracted from umbilical cord tissue, and the basic biological properties and multilineage differentiation potential were examined. Second, 1 × 106 hUC-MSCs were administered intravenously to AIH mice. At the peak of the disease, serum levels of alanine aminotransferase and aspartate aminotransferase and pathologic damage to liver tissue were measured to evaluate liver function and degree of inflammation. We also observed that the infiltration of CD4+ T cells in the liver was significantly reduced. Furthermore, the frequency of the splenic IFNγ- and IL-17A- producing CD4+ T cells were also significantly decreased, while we only observed an increasing trend in Treg cells in liver tissue. Third, an RNA sequencing analysis of liver tissue was performed, which showed that in the UC-MSC-treated group, the transcriptional profiles of inflammation-related signaling pathways were significantly negatively regulated compared to those of phosphate-buffered saline-treated mice. Collectively, these findings indicated the potential of hUC-MSC to suppress immune responses in immune anomaly mediated liver disease, thus offering a potential clinical option to improve AIH.

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脐带来源的间充质干细胞通过调节小鼠的Th1和Th17细胞反应来减轻S100诱导的自身免疫性肝炎。
目前,自身免疫性肝炎(AIH)的一线治疗仍然是糖皮质激素或免疫抑制剂的联合治疗。然而,激素和免疫抑制治疗会引起严重的副作用,如库欣综合征和骨髓抑制。先前的研究报道了间充质干细胞(MSCs)改善肝脏炎症和纤维化的适用性和安全性。然而,间充质干细胞来源的特征直接导致了对间充质细胞介导的免疫调节机制的不同结论。骨髓来源的MSCs可以通过抑制几种促炎细胞因子和上调肝组织中的PD-L1来发挥免疫抑制作用,以改善S100诱导的AIH模型。目前尚不清楚人脐带来源的MSCs(hUC MSCs)是否能直接抑制肝脏炎症,并最终缓解AIH模型中肝细胞的功能障碍。首先,从脐带组织中提取hUC-MSCs,并检测其基本生物学特性和多谱系分化潜力。第二,1 × 将106个hUC-MSC静脉注射给AIH小鼠。在疾病高峰期,测量血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶的水平以及肝组织的病理损伤,以评估肝功能和炎症程度。我们还观察到CD4+T细胞在肝脏中的浸润显著减少。此外,脾脏产生IFNγ和IL-17A的CD4+T细胞的频率也显著降低,而我们只观察到肝组织中Treg细胞的增加趋势。第三,对肝组织进行了RNA测序分析,结果表明,在UC MSC处理组中,与磷酸盐缓冲盐水处理的小鼠相比,炎症相关信号通路的转录谱显著负调控。总之,这些发现表明hUC-MSC在免疫异常介导的肝病中抑制免疫反应的潜力,从而为改善AIH提供了潜在的临床选择。
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来源期刊
Stem Cells International
Stem Cells International CELL & TISSUE ENGINEERING-
CiteScore
8.10
自引率
2.30%
发文量
188
审稿时长
18 weeks
期刊介绍: Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials. Topics covered include, but are not limited to: embryonic stem cells; induced pluripotent stem cells; tissue-specific stem cells; stem cell differentiation; genetics and epigenetics; cancer stem cells; stem cell technologies; ethical, legal, and social issues.
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