TY - JOUR T1 - Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media. JF - Stem Cell Res Ther Y1 - 2014 A1 - Valencic, Erica A1 - Loganes, Claudia A1 - Cesana, Stefania A1 - Piscianz, Elisa A1 - Gaipa, Giuseppe A1 - Biagi, Ettore A1 - Tommasini, Alberto KW - CD4-Positive T-Lymphocytes KW - CD8-Positive T-Lymphocytes KW - Cell Proliferation KW - Cell Survival KW - Cells, Cultured KW - Coculture Techniques KW - Culture Media, Conditioned KW - Cytokines KW - Humans KW - Killer Cells, Natural KW - Lymphocyte Activation KW - Mesenchymal Stromal Cells AB -

INTRODUCTION: 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.

VL - 5 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24405828?dopt=Abstract ER -