amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis羊膜上皮细胞从人类胎盘强有力地抑制小鼠模型的多发性硬化症.pdfVIP

Amniotic Epithelial Cells from the Human Placenta Potently Suppress a Mouse Model of Multiple Sclerosis 1 2 2 1 1 1 Yu Han Liu , Vijesh Vaghjiani , Jing Yang Tee , Kelly To , Peng Cui , Ding Yuan Oh , 2 1 1 Ursula Manuelpillai , Ban-Hock Toh , James Chan * 1 Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia, 2 Center for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia, Abstract 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- b (TGF-b) for immunosuppression. Neutralization of TGF- b 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 a