Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.
PLoS One. 2012;7(4):e35758. doi: 10.1371/journal.pone.0035758. Epub 2012 Apr 26.
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.
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，我们表明 hAEC 可显著抑制体外脾细胞增殖，并有效减弱多发性硬化症（MS）的小鼠模型。hAEC 治疗可显著减少中枢神经系统（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。在脾细胞增殖实验中中和 TGF-β 或 PGE2 可显著降低 hAEC 诱导的抑制作用。hAEC 处理后的脾细胞表现出 Th2 细胞因子偏移，IL-5 产生显著升高。虽然在肺部可以检测到转移的 CFSE 标记的 hAEC，但在 CNS 或淋巴器官中均未检测到。这是首例报道 hAEC 在 MS 样模型中具有治疗作用的报告，并表明 hAEC 可能具有用于 MS 治疗的潜力。
