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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2018-06-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844017339609
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spelling 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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