Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles
Adverse remodeling after myocardial infarction (MI) is strongly influenced by T cells. Stem cell therapy after MI, using mesenchymal stem cells (MSC) or cardiomyocyte progenitor cells (CMPC), improved cardiac function, despite low cell retention and limited differentiation. As MSC secrete many facto...
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doaj-0c1c323fdd4649cc85526802f833fb7e2020-11-25T02:14:04ZengElsevierHeliyon2405-84402018-06-0146e00642Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesiclesF. van den Akker0K.R. Vrijsen1J.C. Deddens2J.W. Buikema3M. Mokry4L.W. van Laake5P.A. Doevendans6J.P.G. Sluijter7Department of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The NetherlandsDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The NetherlandsDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The NetherlandsDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The NetherlandsDivision of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, The NetherlandsDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The NetherlandsDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The Netherlands; ICIN – Netherlands Heart Institute, Utrecht, The NetherlandsDepartment of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, The Netherlands; ICIN – Netherlands Heart Institute, Utrecht, The Netherlands; UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, The Netherlands; Corresponding author.Adverse remodeling after myocardial infarction (MI) is strongly influenced by T cells. Stem cell therapy after MI, using mesenchymal stem cells (MSC) or cardiomyocyte progenitor cells (CMPC), improved cardiac function, despite low cell retention and limited differentiation. As MSC secrete many factors affecting T cell proliferation and function, we hypothesized the immune response could be affected as one of the targets of stem cell therapy. Therefore, we studied the immunosuppressive properties of human BM-MSC and CMPC and their extracellular vesicles (EVs) in co-culture with activated T cells. Proliferation of T cells, measured by carboxyfluorescein succinimidyl ester dilution, was significantly reduced in the presence of BM-MSC and CMPC. The inflammatory cytokine panel of the T cells in co-culture, measured by Luminex assay, changed, with strong downregulation of IFN-gamma and TNF-alpha. The effect on proliferation was observed in both direct cell contact and transwell co-culture systems. Transfer of conditioned medium to unrelated T cells abrogated proliferation in these cells. EVs isolated from the conditioned medium of BM-MSC and CMPC prevented T cell proliferation in a dose-dependent fashion. Progenitor cells presence induces up- and downregulation of multiple previously unreported pathways in T cells. In conclusion, both BM-MSC and CMPC have a strong capacity for in vitro immunosuppression. This effect is mediated by paracrine factors, such as extracellular vesicles. Besides proliferation, many additional pathways are influenced by both BM-MSC and CMPC.http://www.sciencedirect.com/science/article/pii/S2405844017339609ImmunologyStem cell research |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
F. van den Akker K.R. Vrijsen J.C. Deddens J.W. Buikema M. Mokry L.W. van Laake P.A. Doevendans J.P.G. Sluijter |
spellingShingle |
F. van den Akker K.R. Vrijsen J.C. Deddens J.W. Buikema M. Mokry L.W. van Laake P.A. Doevendans J.P.G. Sluijter Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles Heliyon Immunology Stem cell research |
author_facet |
F. van den Akker K.R. Vrijsen J.C. Deddens J.W. Buikema M. Mokry L.W. van Laake P.A. Doevendans J.P.G. Sluijter |
author_sort |
F. van den Akker |
title |
Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles |
title_short |
Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles |
title_full |
Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles |
title_fullStr |
Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles |
title_full_unstemmed |
Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles |
title_sort |
suppression of t cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2018-06-01 |
description |
Adverse remodeling after myocardial infarction (MI) is strongly influenced by T cells. Stem cell therapy after MI, using mesenchymal stem cells (MSC) or cardiomyocyte progenitor cells (CMPC), improved cardiac function, despite low cell retention and limited differentiation. As MSC secrete many factors affecting T cell proliferation and function, we hypothesized the immune response could be affected as one of the targets of stem cell therapy. Therefore, we studied the immunosuppressive properties of human BM-MSC and CMPC and their extracellular vesicles (EVs) in co-culture with activated T cells. Proliferation of T cells, measured by carboxyfluorescein succinimidyl ester dilution, was significantly reduced in the presence of BM-MSC and CMPC. The inflammatory cytokine panel of the T cells in co-culture, measured by Luminex assay, changed, with strong downregulation of IFN-gamma and TNF-alpha. The effect on proliferation was observed in both direct cell contact and transwell co-culture systems. Transfer of conditioned medium to unrelated T cells abrogated proliferation in these cells. EVs isolated from the conditioned medium of BM-MSC and CMPC prevented T cell proliferation in a dose-dependent fashion. Progenitor cells presence induces up- and downregulation of multiple previously unreported pathways in T cells. In conclusion, both BM-MSC and CMPC have a strong capacity for in vitro immunosuppression. This effect is mediated by paracrine factors, such as extracellular vesicles. Besides proliferation, many additional pathways are influenced by both BM-MSC and CMPC. |
topic |
Immunology Stem cell research |
url |
http://www.sciencedirect.com/science/article/pii/S2405844017339609 |
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