title: Human amniotic epithelial cells suppress relapse of corticosteroid-remitted experimental autoimmune disease.
abstract: OBJECTIVE
  Multiple sclerosis (MS) is considered to be a T-cell-mediated disease. Although MS remits with corticosteroid treatment, the disease relapses on discontinuation of therapy. Human amniotic epithelial cells (hAEC) from the placenta are readily accessible in large quantities and have anti-inflammatory properties. Previously we reported that hAEC given near disease onset ameliorated clinical signs and decreased myelin oligodendrocyte glycoprotein (MOG)-specific immune responses in MOG-induced experimental autoimmune encephalomyelitis (EAE), an experimental MS model.
  
  
  METHODS
  To examine the therapeutic effect of hAEC in a clinically relevant setting, we first treated MOG peptide-induced EAE mice with a corticosteroid, prednisolone, in drinking water to induce remission. hAEC were then infused intravenously into the remitted mice. Anti-MOG antibodies in serum were detected by enzyme-linked immunoassay. Splenocyte proliferation was assessed by (3)H-thymidine incorporation. Immune cell subpopulations in spleens and lymph nodes and secreted cytokines in splenocyte culture were quantified by flow cytometry. Central nervous system histology was examined with the use of hematoxylin and eosin, Luxol fast blue and immunostaining.
  
  
  RESULTS
  With cessation of prednisolone treatment, hAEC delayed EAE relapse for 7 days, and, after another 7 days, largely remitted disease in six of eight responder mice. Splenocyte proliferation was suppressed, anti-MOG35-55 antibodies in serum were decreased and interleukin-2 and interleukin-5 production by splenocytes were elevated after hAEC treatment. In the central nervous system, hAEC-treated mice had decreased demyelination and fewer macrophages in the inflammatory infiltrates. hAEC treatment also increased CD4(+)CD25(+)FoxP3(+) regulatory T cells in inguinal lymph nodes.
  
  
  CONCLUSIONS
  These data demonstrate that the therapeutic effects of hAEC after corticosteroid treatment in an MS model probably are the consequence of peripheral immunoregulation. We suggest that hAEC may have potential as a cell therapy for remitted MS.
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: yu-han.liu@monash.edu.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Chan
authors.affiliation: Centre for Genetic Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
authors.forename: Vijesh
authors.initials: V
authors.lastname: Vaghjiani
authors.affiliation: Department of Obstetrics & Gynecology, University of Melbourne and Department of Perinatal Medicine, Pregnancy Research Centre, Royal Women's Hospital, Melbourne, Victoria, Australia.
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
authors.affiliation: Centre for Genetic Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
authors.forename: Ursula
authors.initials: U
authors.lastname: Manuelpillai
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Ban-Hock
authors.initials: BH
authors.lastname: Toh
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D004847:Epithelial Cells / Q000166:cytology / Q000637:transplantation*; D005260:Female; D006801:Humans; D051379:Mice; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000378:metabolism; D010920:Placenta / Q000166:cytology; D011239:Prednisolone / Q000008:administration & dosage; D011247:Pregnancy
chemical_list: D000888:Antibodies, Anti-Idiotypic; D063308:Myelin-Oligodendrocyte Glycoprotein; D011239:Prednisolone
keywords: amniotic epithelial cells; corticosteroids; experimental autoimmune encephalomyelitis; immunosuppression; multiple sclerosis; regulatory T cells