title: Proteome analysis of post-transplantation recovery mechanisms of an EAE model of multiple sclerosis treated with embryonic stem cell-derived neural precursors.
abstract: Multiple sclerosis (MS) is a chronic inflammatory and progressive disorder of the central nervous system (CNS), which ultimately causes demyelination and subsequent axonal injury. Experimental autoimmune encephalomyelitis (EAE) is a well-characterized animal model to study the etiology and pathogenesis of MS. This model can also be used to investigate various therapeutic approaches for MS. Herein; we have treated a score 3 EAE mouse model with an embryonic stem cell-derived neural precursor. Clinical analysis showed recovery of the EAE model of MS following transplantation. We analyzed the proteome of spinal cords of healthy and EAE samples before and after transplantation. Proteome analysis revealed that expressions of 86 spinal cord protein spots changed in the EAE or transplanted mouse compared to controls. Mass spectrometry resulted in identification of 72 proteins. Of these, the amounts of 27 differentially expressed proteins in EAE samples returned to sham levels after transplantation, suggesting a possible correlation between changes at the proteome level and clinical signs of EAE in transplanted mice. The recovered proteins belonged to various functional groups that included disturbances in ionic and neurotransmitter release, apoptosis, iron hemostasis, and signal transduction. Our results provided a proteomic view of the molecular mechanisms of EAE recovery after stem cell transplantation.
  
  
  CONCLUSIONS
  In this study, we applied proteomics to analyze the changes in proteome pattern of EAE mouse model after embryonic stem cell-derived neural precursor transplantation. Our proteome results clearly showed that the expression levels of several differentially expressed proteins in EAE samples returned to sham levels after transplantation, which suggested a possible correlation between changes at the proteome level and decreased clinical signs of EAE in transplanted mice. These results will serve as a basis to address new questions and design new experiments to elucidate the biology of EAE and recovery after transplantation. A thorough understanding of stem cell-mediated therapeutic mechanisms might result in the development of more efficacious therapies for MS than are currently available.
authors.affiliation: Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
authors.forename: Abolhassan Shahzadeh
authors.initials: AS
authors.lastname: Fazeli
authors.forename: Davood
authors.initials: D
authors.lastname: Nasrabadi
authors.forename: Alireza
authors.initials: A
authors.lastname: Pouya
authors.forename: Shahaboodin
authors.initials: S
authors.lastname: Mirshavaladi
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Sanati
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
mesh_terms: D064591:Allografts; D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000628:therapy; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000378:metabolism / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D033581:Stem Cell Transplantation
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome
keywords: EAE; Embryonic stem cells; Multiple sclerosis; Neural progenitors; Proteomics; Transplantation