PMID- 21954834 OWN - NLM STAT- MEDLINE DCOM- 20120423 LR - 20211203 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 14 IP - 1 DP - 2012 Jan TI - Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression. PG - 70-9 LID - 10.3109/14653249.2011.613926 [doi] AB - BACKGROUND AIMS: 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. FAU - Yang, Heung-Mo AU - Yang HM AD - Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Sung, Ji-Hye AU - Sung JH FAU - Choi, Young-Sil AU - Choi YS FAU - Lee, Hyun-Joo AU - Lee HJ FAU - Roh, Cheong-Rae AU - Roh CR FAU - Kim, Jongman AU - Kim J FAU - Shin, Milljae AU - Shin M FAU - Song, Sanghyun AU - Song S FAU - Kwon, Choon-Hyuck AU - Kwon CH FAU - Joh, Jae-Won AU - Joh JW FAU - Kim, Sung-Joo AU - Kim SJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110928 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Antibodies, Blocking) RN - 0 (HLA-G Antigens) RN - 0 (Receptors, Fc) SB - IM MH - Adipose Tissue/cytology/immunology MH - Antibodies, Blocking/pharmacology MH - Cell Differentiation/drug effects/genetics MH - Cells, Cultured MH - Coculture Techniques MH - Gene Expression Regulation, Developmental/drug effects/genetics MH - HLA-G Antigens/genetics/*metabolism MH - Humans MH - Immune Tolerance/drug effects/genetics MH - *Immunosuppression Therapy MH - Leukocytes, Mononuclear/immunology/metabolism MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/drug effects/*immunology MH - *Organ Transplantation MH - Receptors, Fc/immunology MH - Transgenes/genetics EDAT- 2011/10/01 06:00 MHDA- 2012/04/24 06:00 CRDT- 2011/09/30 06:00 PHST- 2011/09/30 06:00 [entrez] PHST- 2011/10/01 06:00 [pubmed] PHST- 2012/04/24 06:00 [medline] AID - S1465-3249(12)70616-3 [pii] AID - 10.3109/14653249.2011.613926 [doi] PST - ppublish SO - Cytotherapy. 2012 Jan;14(1):70-9. doi: 10.3109/14653249.2011.613926. Epub 2011 Sep 28.