title: Immunomodulatory effects of mice mesenchymal stem cells on maturation and activation of dendritic cells.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) possess a wide range of immunomodulatory functions mostly in immune cells including dendritic cells (DCs). DCs are the key cells in the immune response and play an important role in initiating cell-mediated immunity.
  
  
  OBJECTIVE
  To evaluate the immunomodulatory effects of MSCs supernatant on maturation and function of DCs.
  
  
  METHODS
  Bone marrow derived mice MSCs were isolated and cultured. Twenty-four, forty-eight and seventy-two hours after passage 6, supernatants were collected and MSCs were assessed by flow cytometric analysis for the expression of CD34, CD44, CD45 and SCA-1. Splenic DCs were isolated using MACS and then co-cultured with MSCs supernatant. Expression of CD86, CD40 and MHC-II on DCs were also evaluated by flow cytometry. H3-thymidine incorporation by proliferating T cells was determined in two separate MLR assay settings. In one setting, DCs were co-cultured with T cells in the presence of MSCs supernatant, and in the other setting DCs were treated with MSCs supernatant and then were co-cultured with T cells. Production of IL-12, IL-6 and IL-10 cytokines was measured in the supernatant of DCs treated with MSCs supernatant. We also measured IFN-γ and IL-4 levels in MLR supernatant.
  
  
  RESULTS
  The results showed that 72h MSCs supernatant could decrease the expression of MHC-II and CD86. The T cell proliferation was inhibited in the presence of MSCs supernatant and MSCs supernatant treated DCs as demonstrated by MLR assay. A significant increase in IL-4 level and a non significant decrease in IFN-γ level in MLR supernatant was observed. However, IL-6, IL-10 and IL-12 production did not change significantly.
  
  
  CONCLUSIONS
  MSCs supernatant has a time dependent effect on the maturation of DCs. Also, it could alter cytokine production from responding T cells toward Th2. Generally, the findings of this study supported the immunomodulatory effect of MSCs supernatant on DCs maturation and function.
authors.affiliation: Department of Biology, Islamic Azad University, Fars Science and Research Branch, Shiraz, Iran.
authors.forename: Ladan
authors.initials: L
authors.lastname: Sadeghi
authors.forename: Eskandar
authors.initials: E
authors.lastname: Kamali-Sarvestani
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Shariati
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Karimi
mesh_terms: D050156:Adipogenesis; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D056747:Immunomodulation; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D010012:Osteogenesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D017077:Culture Media, Conditioned; D016207:Cytokines