Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice.
Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice.
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DOI：
10.1186/s12967-014-0344-5
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发表时间：
2014-12-05
影响因子：
7.4
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Lv Y;Xu X;Zhang B;Zhou G;Li H;Du C;Han H;Wang H
子宫内膜再生细胞（ERC）是间充质样干细胞，其可以非侵入性地从月经血中获得，并且容易大规模生长/产生而没有肿瘤发生。我们以前报道过ERCs在体外表现出独特的免疫调节特性，但是它们在保护结肠免受结肠炎方面的免疫抑制潜力尚未被研究。本研究旨在确定ERCs介导免疫调节功能对抗结肠炎的疗效。用4%葡聚糖硫酸钠（DSS，在饮用水中）在BALB/c小鼠中诱导结肠炎7天。从健康雌性月经血培养ERCs，并注射（1百万只/小鼠/天，i. v.）在结肠炎诱导后的第2、5和8天，在DSS诱导后第14天收集结肠和脾组织。评估临床体征、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。DSS诱导的未治疗组小鼠出现严重的结肠炎，表现为体重减轻、血便、腹泻、粘膜溃疡和结肠缩短，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减轻结肠炎，显著降低DAI，降低结肠内IL-2和TNF-α的水平，但增加IL-4和IL-10的表达。与未治疗的结肠炎小鼠相比，从ERC治疗的小鼠中分离的脾脏树突状细胞表现出显着降低MHC-II表达。经ERC处理的小鼠还表现出更少的CD 3 + CD 25+活性T细胞和CD 3 + CD 8 + T细胞群体以及显著更高水平的CD 4 + CD 25 + Foxp 3 + Treg细胞。这项研究证明了ERC在减轻小鼠结肠炎中的新型抗炎和免疫抑制作用，并表明ERC的独特功能使其成为治疗溃疡性结肠炎的有前途的治疗工具。
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.
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影响因子：
4.3
作者：
Chen, Lin-Lin;Wang, Xue-Hong;Lu, Fang-Gen
通讯作者：
Lu, Fang-Gen
影响因子：
1.3
作者：
Iyer SS;Cheng G
通讯作者：
Cheng G
影响因子：
4
作者：
Borlongan, Cesar V.;Kaneko, Yuji;Sanberg, Paul R.
通讯作者：
Sanberg, Paul R.
DOI：
10.1124/jpet.108.137083
发表时间：
2008-08-01
影响因子：
3.5
作者：
Hayashi, Yujiro;Tsuji, Shingo;Kawano, Sunao
通讯作者：
Kawano, Sunao
影响因子：
2.6
作者：
Le Blanc, K;Tammik, C;Ringdén, O
通讯作者：
Ringdén, O