title: The TLR7 agonist Imiquimod promote the immunogenicity of mesenchymal stem cells.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) are considered the best candidate in stem cells therapy due to their multipotent differentiation ability, low expression of co-stimulatory molecules (CD80, CD86, CD34 and HLA-II) and immunosuppression effects on in vivo immune responses. MSCs were now widely used in clinical trials but received no encourage results. The major problem was the fate of engrafted MSCs in vivo could not be defined. Some studies indicated that MSCs could induce immune response and result in the damage and rejection of MSCs. As toll like receptors (TLRs) are important in inducing of immune responses, in this study we study the role of TLR7 in mediating the immune status of MSCs isolated from umbilical cord.
  
  
  RESULTS
  Our results indicated that TLR7 agonist Imiquimod could increase the proliferation of PBMC isolated from healthy human volunteers and release of lactate dehydrogenase (LDH) in supernatant from PBMC-UCMSCs co-culture system. Flow cytometry and quantitative PCR also confirmed the regulated expression of surface co-stimulatory molecules and pro-inflammatory genes (IL-6, IL-8, IL-12, TGF-β and TNF-α). And the down-regulation expression of stem cell markers also confirmed the loss of stemness of UCMSCs. We also found that the osteo-differentiation ability of UCMSCs was enhanced in the presence of Imiquimod.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report that activation of TLR7 pathway increases the immunogenicity of UCMSCs. Extensive researches have now been conducted to study whether the change of immune status will be help in tumor rejection based on the tumor-tropism of MSCs.
authors: Li
authors: L
authors: Zhang
authors: Dan
authors: D
authors: Liu
authors: Dan
authors: D
authors: Pu
authors: Yanwen
authors: Y
authors: Wang
authors: Li
authors: L
authors: Li
authors: Yanqi
authors: Y
authors: He
authors: Yalun
authors: Y
authors: Li
authors: Lei
authors: L
authors: Li
authors: Weimin
authors: W
authors: Li
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008565:Membrane Proteins / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology*; D010012:Osteogenesis / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D015703:Antigens, CD; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007770:L-Lactate Dehydrogenase; D000077271:Imiquimod
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