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Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055165/ https://www.ncbi.nlm.nih.gov/pubmed/24405828 http://dx.doi.org/10.1186/scrt392 |
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author | Valencic, Erica Loganes, Claudia Cesana, Stefania Piscianz, Elisa Gaipa, Giuseppe Biagi, Ettore Tommasini, Alberto |
author_facet | Valencic, Erica Loganes, Claudia Cesana, Stefania Piscianz, Elisa Gaipa, Giuseppe Biagi, Ettore Tommasini, Alberto |
author_sort | Valencic, Erica |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4055165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40551652014-06-15 Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media Valencic, Erica Loganes, Claudia Cesana, Stefania Piscianz, Elisa Gaipa, Giuseppe Biagi, Ettore Tommasini, Alberto Stem Cell Res Ther Research 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. BioMed Central 2014-01-09 /pmc/articles/PMC4055165/ /pubmed/24405828 http://dx.doi.org/10.1186/scrt392 Text en Copyright © 2014 Valencic et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Valencic, Erica Loganes, Claudia Cesana, Stefania Piscianz, Elisa Gaipa, Giuseppe Biagi, Ettore Tommasini, Alberto Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
title | Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
title_full | Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
title_fullStr | Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
title_full_unstemmed | Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
title_short | Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
title_sort | inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055165/ https://www.ncbi.nlm.nih.gov/pubmed/24405828 http://dx.doi.org/10.1186/scrt392 |
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