title: Influence of inflammation on the immunological profile of adult-derived human liver mesenchymal stromal cells and stellate cells.
abstract: OBJECTIVE
  Stem cell therapy for liver diseases has recently emerged as a promising alternative to liver transplantation. Eligible cells should have an appropriate immunophenotype. The aim of the present study was to define the immunological profile of two human liver-derived mesenchymal stromal cell populations, namely, stem cells (ADHLSC) and hepatic stellate cells (HSC).
  
  
  METHODS
  The study was conducted under normal and inflammatory conditions with the use of human bone marrow mesenchymal stromal cells (BM-MSC) as reference.
  
  
  RESULTS
  Like BM-MSC and ADHLSC, HSC were negative for hematopoietic (CD45) and endothelial (CD34) markers but positive for stromal markers. All cell types were constitutively positive for HLA class I and negative for human leukocyte antigen (HLA) class II and co-stimulatory molecules (CD80, CD86, CD134 and CD252). Inflammation induced the expression of CD40 in all cell types, but the highest values were observed on HSCs; high CD252 expression was only observed on HSC as compared with ADHLSC and BM-MSC. The expression of various adhesion molecules (CD54, CD58, CD106 and CD166) was dissimilar in these three cell types and was differentially influenced by inflammation as well. ADHLSC and HSC constitutively expressed the immunosuppressive molecule HLA-G, whereas CD274 expression was induced by inflammation, as in the case of BM-MSC. Moreover, all cell types expressed the two major natural killer ligands CD112 and CD115.
  
  
  CONCLUSIONS
  Toll-like receptors (TLR) 1, 3, 4 and 6 messenger RNA was expressed by both cell types, whereas TLR 2, 5, 7, 9 and 10 were only expressed by ADHLSC. Inflammation increased the expression of TLR 2 and 3 by ADHLSC and HSC. Finally, both liver-derived cell types were immunosuppressive because they inhibited the proliferation of mitogen-activated T cells.
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: gordana.raicevic@ulb.ac.be.
authors.forename: Gordana
authors.initials: G
authors.lastname: Raicevic
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
authors.affiliation: Laboratory of Pediatric Hepatology and Cell Therapy, Institute of Experimental & Clinical Research, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.affiliation: Liver Cell Biology Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Adil
authors.initials: A
authors.lastname: El Taghdouini
authors.affiliation: Liver Cell Biology Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
authors.affiliation: Laboratory of Pediatric Hepatology and Cell Therapy, Institute of Experimental & Clinical Research, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Toungouz
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D064987:Cell- and Tissue-Based Therapy; D059951:HLA-G Antigens / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology*; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000166:cytology; D008107:Liver Diseases / Q000628:therapy; D008213:Lymphocyte Activation / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051193:Toll-Like Receptors / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; D060890:B7-H1 Antigen; D015415:Biomarkers; D059951:HLA-G Antigens; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D051193:Toll-Like Receptors; D016186:Receptor, Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens
keywords: Toll-like receptors; adult-derived human liver stem cells; cell adhesion molecules; inflammation; stellate cells