Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis

Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis
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DOI:
10.3748/wjg.v21.i7.2030
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发表时间:
2015-02-21
影响因子:
4.3
通讯作者:
Cho, Seok-Goo
Cho, Seok-Goo
中科院分区:
医学2区
文献类型:
--
作者:
Nam, Young-Sun;Kim, Nayoun;Cho, Seok-Goo

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目的:目的:探讨骨髓间充质干细胞(MSCs)对葡聚糖硫酸钠诱导的炎症性肠病(IBD)的影响。在第七天,小鼠接受I X IO 6个MSC的腹膜内注射。每天监测存活率、疾病活动指数值和体重。在第十天,评估结肠长度和组织病理学变化。此外,免疫调节的变化后,MSC管理进行了评估,通过确定脾脏和肠系膜淋巴结中的效应T细胞反应的水平,和炎症细胞因子的表达水平在均质colons.RESULTS:腹腔内给药的MSC并没有阻止结肠炎的发展,并没有减少IBD的临床病理严重程度。对照组和MSC治疗组之间的生存率或疾病活动指数评分无显著差异。第10天处死的小鼠在结肠长度或组织病理学发现方面均未表现出显著差异。事实上,MSC治疗组在脾脏、肠系膜淋巴结和均质结肠中表现出白细胞介素(IL)-6和转化生长因子-β水平升高,而IL-10水平降低。MSC治疗组肠系膜淋巴结中IL-17水平较低(P = 0.0126)。在均质结肠,IL-17和肿瘤坏死因子-α(P = 0.0092)的表达水平也较低,在治疗group.CONCLUSION:MSC输注没有提供显着的组织病理学或临床改善,从而代表一个有限的治疗方法IBD。MSCs的功能增强有待于进一步研究。
AIM: To investigate the effects of mesenchymal stem cells (MSCs) on dextran sulfate sodium-induced inflammatory bowel disease (IBD).METHODS: C57BL/6 mice were fed 3.5% (g/L) dextran sulfate sodium. On day seven, the mice received intraperitoneal injections of 1 x 106 MSCs. The survival rate, disease activity index values, and body weight, were monitored daily. On day ten, colon lengths and histopathologic changes were assessed. In addition, immunoregulatory changes following MSC administration were evaluated by determining the levels of effector T cell responses in the spleen and mesenteric lymph nodes, and the expression levels of inflammatory cytokines in homogenized colons.RESULTS: Intraperitoneal administration of MSCs did not prevent development of colitis and did not reduce the clinicopathologic severity of IBD. No significant difference was evident in either survival rate or disease activity index score between the control and MSC-treated group. Day ten-sacrificed mice exhibited no significant difference in either colon length or histopathologic findings. Indeed, the MSC-treated group exhibited elevated levels of interleukin (IL)-6 and transforming growth factor-beta, and a reduced level of IL-10, in spleens, mesenteric lymph nodes, and homogenized colons. The IL-17 level was lower in the mesenteric lymph nodes of the MSC-treated group (P = 0.0126). In homogenized colons, the IL-17 and tumor necrosis factor-alpha (P = 0.0092) expression levels were also lower in the treated group.CONCLUSION: MSC infusion provided no significant histopathologic or clinical improvement, thus representing a limited therapeutic approach for IBD. Functional enhancement of MSCs is needed in further study.