title: Amniotic epithelial cells from the human placenta potently suppress a mouse model of multiple sclerosis.
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-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.
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia.
authors.forename: Yu Han
authors.initials: YH
authors.lastname: Liu
authors.forename: Vijesh
authors.initials: V
authors.lastname: Vaghjiani
authors.forename: Jing Yang
authors.initials: JY
authors.lastname: Tee
authors.forename: Kelly
authors.initials: K
authors.lastname: To
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.forename: Ding Yuan
authors.initials: DY
authors.lastname: Oh
authors.forename: Ursula
authors.initials: U
authors.lastname: Manuelpillai
authors.forename: Ban-Hock
authors.initials: BH
authors.lastname: Toh
authors.forename: James
authors.initials: J
authors.lastname: Chan
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016207:Cytokines; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D015232:Dinoprostone