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人脂肪来源干细胞减轻白细胞介素-10基因敲除小鼠的炎症性肠病。

Human adipose-derived stem cells attenuate inflammatory bowel disease in IL-10 knockout mice.

作者信息

Jung Woo Yeun, Kang Joo Hwan, Kim Kyung Gon, Kim Hee Snn, Jang Byung Ik, Park Yong Hoon, Song In-Hwan

机构信息

Department of Anatomy, Yeungnam University College of Medicine, 170, Hyeonchung-ro, Nam-gu, Daegu, 705-717, Republic of Korea.

Department of Microbiology, Yeungnam University College of Medicine, 170, Hyeonchung-ro, Nam-gu, Daegu, 705-717, Republic of Korea.

出版信息

Tissue Cell. 2015 Feb;47(1):86-93. doi: 10.1016/j.tice.2014.12.001. Epub 2014 Dec 6.

DOI:10.1016/j.tice.2014.12.001
PMID:25544730
Abstract

Inflammatory bowel disease (IBD) is a complex immunological disorder characterized by chronic inflammation caused mainly by unknown factors. The interleukin-10 knockout (IL-10 KO) mouse is a well-established murine model of IBD which develops spontaneous intestinal inflammation that resembles Crohn's disease. In the present study, human adipose-derived mesenchymal stem cells (hAMSCs) were administrated to IL-10 KO mice to evaluate the anti-inflammatory effects of hAMSCs that may attenuate the progress of or treat IBD. After IBD was induced by feeding the IL-10 KO mouse a 125-250 ppm piroxicam mixed diet for 1 week, 2×10(6) hAMSCs were injected into the peritoneum and the mice were switched to a normal diet. After 1 week, the mice were sacrificed and tissue samples were harvested. Tissue scores for inflammation and inflammation-related genes expression were determined. The hAMSC-treated group showed significantly reduced inflammatory changes in histological analysis. Reverse transcription-PCR analysis showed that RANTES, Toll-like receptor 9, and IL-4 expression levels were not significantly different between the groups while IL-12, INF-γ, and TNF-α levels were significantly decreased in the hAMSC treated group. hAMSC attenuated IBD in the IL-10 KO mice by suppressing inflammatory cytokine expression, was mediated by the type 1 helper T cell pathway. Even though only a single injection of hAMSCs was delivered, the effect influenced chronic events associated with inflammatory changes and demonstrated that hAMSCs are a powerful candidate for IBD therapy.

摘要

炎症性肠病(IBD)是一种复杂的免疫紊乱疾病,其特征为主要由未知因素引起的慢性炎症。白细胞介素10基因敲除(IL-10 KO)小鼠是一种成熟的IBD小鼠模型,可自发发生类似于克罗恩病的肠道炎症。在本研究中,将人脂肪来源的间充质干细胞(hAMSCs)给予IL-10 KO小鼠,以评估hAMSCs可能减轻IBD进展或治疗IBD的抗炎作用。在用含125 - 250 ppm吡罗昔康的混合饮食喂养IL-10 KO小鼠1周诱导IBD后,将2×10(6)个hAMSCs注入腹膜,然后将小鼠改为正常饮食。1周后,处死小鼠并采集组织样本。测定炎症组织评分和炎症相关基因表达。hAMSC治疗组在组织学分析中显示炎症变化显著减少。逆转录 - PCR分析表明,各组之间RANTES、Toll样受体9和IL-4的表达水平无显著差异,而hAMSC治疗组中IL-12、INF-γ和TNF-α水平显著降低。hAMSC通过抑制炎症细胞因子表达减轻IL-10 KO小鼠的IBD,这是由1型辅助性T细胞途径介导的。尽管只注射了一次hAMSCs,但其效果影响了与炎症变化相关的慢性事件,并表明hAMSCs是IBD治疗的有力候选者。

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