Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice
Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice
复制标题
骨髓间充质干细胞可改善小鼠结肠炎相关的肿瘤发生。
DOI：
10.1016/j.bbrc.2014.07.002
复制
发表时间：
2014-08-08
影响因子：
3.1
通讯作者：
Lan, Ping
中科院分区：
文献类型：
--
作者：
Chen, Zexian;He, Xiaowen;Lan, Ping
背景和目的：骨髓间充质干细胞(MSC)在炎症性肠病(IBD)的基础和临床研究中得到了广泛的研究。然而，IBD患者发生结直肠癌的风险更高，MSC对肿瘤的发生具有双重作用。本研究旨在探讨骨髓间充质干细胞在IBD发病中的作用。方法：从同种异体小鼠骨髓中分离MSCs，用流式细胞仪进行鉴定。在以偶氮甲烷和葡聚糖硫酸钠诱导的结肠炎相关肿瘤模型中，注射间充质干细胞。大体观察结肠长度、脾大小和肿瘤形成情况。结果：与PBS对照组相比，MSCs组大鼠结肠炎相关肿瘤的严重程度减轻，体重减轻，结肠变长，脾变小。MSC组的肿瘤数量和肿瘤负荷显著减少，而肿瘤大小保持不变。组织学评估显示，MSCs可减轻结肠组织的组织学损伤。经MSC处理后，大鼠结肠组织中促炎症细胞因子(TNF-α、IL-1β和IL-6)表达减少，STAT3磷酸化水平下调。结论：MSCs可能通过抑制促炎细胞因子表达和STAT3活化而减轻炎症性肠病的发生。(C)2014 Elsevier Inc.保留所有权利。
Background and Aims: Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD.Methods: MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed.Results: MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment.Conclusion: MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation. (C) 2014 Elsevier Inc. All rights reserved.