title: Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) from several tissues have immunomodulatory properties that involve various immunosuppressive molecules. An example is human leukocyte antigen (HLA)-G, a non-classical major histocompatibility complex (MHC) class I molecule that induces tolerance via interactions with inhibitory receptors present on major immune effector cells. Recently, the molecular mechanisms that regulate MSC-mediated immunosuppression have come under investigation. Our goal was to determine whether HLA-G plays a crucial role in immunosuppression and whether human adipose tissure (hAT) MSC can be used as a tool for biologic immunosuppression with HLA-G in transplantation.
  
  
  METHODS
  MSC were characterized by fluorescence-activated cell sorting (FACS) analysis, reverse transcriptase (RT)-polymerase chain reaction (PCR) and staining for differentiation. The immunogenicity and immunomodulatory effects of MSC were monitored by peripheral blood mononuclear cell (PBMC) proliferation assay with or without phytohemagglutinin (PHA) stimulation. Stable expression of HLA-G1 in MSC was done using a lentiviral system. Results. MSC from different tissues had similar morphology, immunophenotypic characters and differentiation potential. We also found that the immunosuppressive effect of MSC was monitored along with their endogenous HLA-G mRNA and protein levels. Stable expression of HLA-G1 appeared to enhance the immunosuppressive effect of hAT MSC, and the function of HLA-G1 was significantly decreased by HLA-G antagonistic antibody in PBMC proliferation assays.
  
  
  CONCLUSIONS
  Although the HLA-G molecule is not the sole factor for MSC-mediated immunosuppression, our data provide evidence that HLA-G plays an important role in immunosuppression and that hAT MSC can be used as a tool for biologic immunosuppression during transplantation procedures.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Heung-Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Sung
authors.forename: Young-Sil
authors.initials: YS
authors.lastname: Choi
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Cheong-Rae
authors.initials: CR
authors.lastname: Roh
authors.forename: Jongman
authors.initials: J
authors.lastname: Kim
authors.forename: Milljae
authors.initials: M
authors.lastname: Shin
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Song
authors.forename: Choon-Hyuck
authors.initials: CH
authors.lastname: Kwon
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Joh
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D019138:Antibodies, Blocking / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics; D007165:Immunosuppression Therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology*; D016377:Organ Transplantation; D011961:Receptors, Fc / Q000276:immunology; D019076:Transgenes / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; D059951:HLA-G Antigens; D011961:Receptors, Fc