Amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis.

Amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis.
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DOI:
10.1371/journal.pone.0035758
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Chan J
Chan J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu YH;Vaghjiani V;Tee JY;To K;Cui P;Oh DY;Manuelpillai U;Toh BH;Chan J

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人羊膜上皮细胞(hAEC)具有干细胞样特征和免疫调节特性。在这里,我们证明 hAEC 在体外显着抑制脾细胞增殖,并有效减弱多发性硬化症 (MS) 小鼠模型。 hAEC 治疗显着减少中枢神经系统 (CNS) CD3+ T 细胞和 F4/80+ 单核细胞/巨噬细胞浸润和脱髓鞘。除了已知的前列腺素 E2 (PGE2) 分泌外,我们还报告了 hAEC 利用转化生长因子-β (TGF-β) 进行免疫抑制的新发现。在脾细胞增殖测定中中和 TGF-β 或 PGE2 可显着减少 hAEC 诱导的抑制。 hAEC 处理小鼠的脾细胞显示 Th2 细胞因子转变,且 IL-5 产量显着升高。虽然可以在肺中检测到转移的 CFSE 标记的 hAEC,但在中枢神经系统或淋巴器官中没有检测到。这是第一份记录 hAEC 在 MS 样模型中的治疗效果的报告,表明 hAEC 可能具有用于治疗 MS 的潜力。
Human amniotic epithelial cells (hAEC) have stem cell-like features and immunomodulatory properties. Here we show that hAEC significantly suppressed splenocyte proliferation in vitro and potently attenuated a mouse model of multiple sclerosis (MS). Central nervous system (CNS) CD3+ T cell and F4/80+ monocyte/macrophage infiltration and demyelination were significantly reduced with hAEC treatment. Besides the known secretion of prostaglandin E2 (PGE2), we report the novel finding that hAEC utilize transforming growth factor-β (TGF-β) for immunosuppression. Neutralization of TGF-β or PGE2 in splenocyte proliferation assays significantly reduced hAEC-induced suppression. Splenocytes from hAEC-treated mice showed a Th2 cytokine shift with significantly elevated IL-5 production. While transferred CFSE-labeled hAEC could be detected in the lung, none were identified in the CNS or in lymphoid organs. This is the first report documenting the therapeutic effect of hAEC in a MS-like model and suggest that hAEC may have potential for use as therapy for MS.
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