Chen Zexian, He Xiaowen, He Xiaosheng, Chen Xiuting, Lin Xutao, Zou Yifeng, Wu Xiaojian, Lan Ping
Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, PR China.
Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, PR China.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1402-8. doi: 10.1016/j.bbrc.2014.07.002. Epub 2014 Jul 7.
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.
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.
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-α, IL-1β and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment.
MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation.
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研究。然而，IBD患者患结直肠癌的风险更高，且MSC对肿瘤发生具有双重作用。本研究旨在评估MSC在IBD肿瘤发生中的作用。
从同种异体小鼠的骨髓中分离出MSCs，并通过流式细胞术进行鉴定。用MSC注射由氧化偶氮甲烷和葡聚糖硫酸钠诱导的结肠炎相关肿瘤发生模型中的小鼠。宏观评估结肠长度、脾脏大小和肿瘤形成情况。分析结肠组织中的促炎细胞因子和STAT3磷酸化情况。
与PBS对照组相比，MSC改善了结肠炎相关肿瘤发生的严重程度，体重减轻减轻，结肠更长，脾脏更小。MSC组的肿瘤数量和肿瘤负荷明显更少，而肿瘤大小保持相当。组织学评估表明，MSC可以减少结肠组织的组织学损伤。MSC治疗后，结肠组织中促炎细胞因子（TNF-α、IL-1β和IL-6）的表达降低，STAT3磷酸化下调。
MSC可能通过抑制促炎细胞因子的表达和STAT3激活来改善炎症性肠病的肿瘤发生。
