title: Mesenchymal stromal cells impair the differentiation of CD14(++) CD16(-) CD64(+) classical monocytes into CD14(++) CD16(+) CD64(++) activate monocytes.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) possess immunomodulatory activity both in vitro and in vivo. However, little information is available regarding their function during the initiation of immunologic responses through their interactions with monocytes. While many studies have shown that MSC impair the differentiation of monocytes into dendritic cells and macrophages, there are few articles showing the interaction between MSC and monocytes and none of them has addressed the question of monocyte subset modulation.
  
  
  METHODS
  To understand better the mechanism behind the benefit of MSC infusion for graft-versus-host treatment through monocyte involvement, we performed mixed leucocyte reactions (MLR) in the presence and absence of MSC. After 3 and 7 days, cultures were analyzed by flow cytometry using different approaches.
  
  
  RESULTS
  MSC induced changes in monocyte phenotype in an MLR. This alteration was accompanied by an increase in monocyte counting and CD14 expression. MSC induced monocyte alterations even without contact, although the parameters above were more pronounced with cell-cell contact. Moreover, the presence of MSC impaired major histocompatibility complex (MHC) I and II, CD11c and CCR5 expression and induced CD14 and CD64 expression on monocytes. These alterations were accompanied by a decrease in interleukin (IL)-1β and IL-6 production by these monocytes, but no change was observed taking into account the phagocytosis capacity of these monocytes.
  
  
  CONCLUSIONS
  Our results suggest that MSC impair the differentiation of CD14(++) CD16(-) CD64(+) classical monocytes into CD14(++) CD16(+) CD64(++) activated monocytes, having an even earlier role than the differentiation of monocytes into dendritic cells and macrophages.
authors.affiliation: Instituto Nacional de Câncer, Centro de Transplante de Medula Óssea, Laboratório de Célula Tronco, Rio de Janeiro, Brazil. barbaradurocher@inca.gov.br
authors.forename: Bárbara
authors.initials: B
authors.lastname: Du Rocher
authors.forename: Andre Luiz
authors.initials: AL
authors.lastname: Mencalha
authors.forename: Bernadete Evangelho
authors.initials: BE
authors.lastname: Gomes
authors.forename: Eliana
authors.initials: E
authors.lastname: Abdelhay
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D056747:Immunomodulation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D053583:Interleukin-1beta; D015850:Interleukin-6; D019713:Receptors, CCR5