Lv Yongcheng, Xu Xiaoxi, Zhang Bai, Zhou Guangying, Li Hongyue, Du Caigan, Han Hongqiu, Wang Hao
Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Tianjin General Surgery Institute, Tianjin, China.
J Transl Med. 2014 Dec 5;12:344. doi: 10.1186/s12967-014-0344-5.
Endometrial regenerative cells (ERCs) are mesenchymal-like stem cells that can be non-invasively obtained from menstrual blood and are easily grown /generated at a large scale without tumorigenesis. We previously reported that ERCs exhibit unique immunoregulatory properties in vitro, however their immunosuppressive potential in protecting the colon from colitis has not been investigated. The present study was undertaken to determine the efficacy of ERCs in mediating immunomodulatory functions against colitis.
Colitis was induced by 4% dextran-sulfate-sodium (DSS, in drinking water) in BALB/c mice for 7 days. ERCs were cultured from healthy female menstrual blood, and injected (1 million/mouse/day, i.v.) into mice on days 2, 5, and 8 following colitis induction. Colonic and splenic tissues were collected on day 14 post-DSS-induction. Clinical signs, disease activity index (DAI), pathological and immunohistological changes, cytokine profiles and cell populations were evaluated.
DSS-induced mice in untreated group developed severe colitis, characterized by body-weight loss, bloody stool, diarrhea, mucosal ulceration and colon shortening, as well as pathological changes of intra-colon cell infiltrations of neutrophils and Mac-1 positive cells. Notably, ERCs attenuated colitis with significantly reduced DAI, decreased levels of intra-colon IL-2 and TNF-α, but increased expressions of IL-4 and IL-10. Compared with those of untreated colitis mice, splenic dendritic cells isolated from ERC-treated mice exhibited significantly decreased MHC-II expression. ERC-treated mice also demonstrated much less CD3(+)CD25(+) active T cell and CD3(+)CD8(+) T cell population and significantly higher level of CD4(+)CD25(+)Foxp3(+) Treg cells.
This study demonstrated novel anti-inflammatory and immunosuppressive effects of ERCs in attenuating colitis in mice, and suggested that the unique features of ERCs make them a promising therapeutic tool for the treatment of ulcerative colitis.
子宫内膜再生细胞（ERCs）是间充质样干细胞，可从月经血中无创获取，且易于大规模培养/生成而不发生肿瘤形成。我们之前报道过ERCs在体外具有独特的免疫调节特性，然而它们在保护结肠免受结肠炎侵害方面的免疫抑制潜力尚未得到研究。本研究旨在确定ERCs介导针对结肠炎的免疫调节功能的功效。
通过在BALB/c小鼠饮用水中给予4%葡聚糖硫酸钠（DSS）诱导结肠炎7天。从健康女性月经血中培养ERCs，并在诱导结肠炎后的第2、5和8天静脉注射（每只小鼠100万个/天）到小鼠体内。在DSS诱导后第14天收集结肠和脾脏组织。评估临床症状、疾病活动指数（DAI）、病理和免疫组织学变化、细胞因子谱和细胞群体。
未治疗组中DSS诱导的小鼠发生了严重的结肠炎，其特征为体重减轻、便血、腹泻、黏膜溃疡和结肠缩短，以及结肠内中性粒细胞和Mac-1阳性细胞浸润的病理变化。值得注意的是，ERCs减轻了结肠炎，DAI显著降低，结肠内IL-2和TNF-α水平降低，但IL-4和IL-10的表达增加。与未治疗的结肠炎小鼠相比，从接受ERCs治疗的小鼠中分离出的脾脏树突状细胞表现出MHC-II表达显著降低。接受ERCs治疗的小鼠还表现出CD3(+)CD25(+)活性T细胞和CD3(+)CD8(+) T细胞群体明显减少，以及CD4(+)CD25(+)Foxp3(+)调节性T细胞水平显著升高。
本研究证明了ERCs在减轻小鼠结肠炎方面具有新的抗炎和免疫抑制作用，并表明ERCs的独特特性使其成为治疗溃疡性结肠炎的有前景的治疗工具。
