title: Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media.
abstract: BACKGROUND
  Despite having a proven immunosuppressive potential in vitro, human mesenchymal stromal cells (MSCs) are reported to display variable efficacy in vivo and, in fact, their proven benefit in the clinical practice is still limited and controversial.
  
  
  METHODS
  The interplay between clinical grade MSCs and pre-activated donor lymphocytes or selected lymphocyte subsets was studied in vitro. The kinetics of MSC growth and viability was evaluated by adhesion-dependent changes of culture plate impedance and biochemically by a colorimetric assay. Activation of natural killer (NK) cells was assessed as well, using a flow cytometry assay.
  
  
  RESULTS
  A strong inhibition of MSC growth was rapidly induced by the addition of pre-activated lymphocytes but not of resting lymphocytes. Inhibition seems not to be attributable to a single cell population, as similar results can be obtained by depleting NK cells or by using either selected CD4+ or CD8+ lymphocytes. In addition, conditioned medium (CM) from activated lymphocytes was able to inhibit MSC growth in a dose-dependent manner. Furthermore, licensing with IFN-γ partially protected MSCs from pre-activated lymphocytes but not from their CM. These results suggest an inhibitory role of lymphocyte-activation-derived substances. However, the identification of a single molecule responsible for MSC inhibition remained elusive, even if preliminary experiments showed that ATP and, to a lesser extent, TNF-α might play a role.
  
  
  CONCLUSIONS
  These results suggest that survival of MSCs can be affected by soluble mediators released by activated lymphocytes. Thus it can be hypothesized that MSC immunosuppressive action in vivo could be impaired by ongoing immune activation through the release of inflammatory mediators.
authors.forename: Erica
authors.initials: E
authors.lastname: Valencic
authors.forename: Claudia
authors.initials: C
authors.lastname: Loganes
authors.forename: Stefania
authors.initials: S
authors.lastname: Cesana
authors.forename: Elisa
authors.initials: E
authors.lastname: Piscianz
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gaipa
authors.forename: Ettore
authors.initials: E
authors.lastname: Biagi
authors.forename: Alberto
authors.initials: A
authors.lastname: Tommasini
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines