Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles

Heliyon
F van den AkkerJ P G Sluijter

Abstract

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 in...Continue Reading

Citations

Oct 1, 2019·Journal of Cellular and Molecular Medicine·Felicia CarotenutoPaolo Di Nardo
Mar 19, 2020·Cells·Carolina BalbiSveva Bollini
Nov 7, 2019·International Journal of Molecular Sciences·Joan Oliva
Dec 19, 2019·Frontiers in Immunology·Marina O GomzikovaAlbert A Rizvanov
May 24, 2020·Journal of Cardiovascular Translational Research·Elise L KesslerSaskia C A de Jager
Feb 4, 2021·International Journal of Molecular Sciences·Hsuan PengAhmed Abdel-Latif
Feb 9, 2021·Frontiers in Bioengineering and Biotechnology·Marietta HerrmannSusanne Grässel
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Riccardo BazzoniMauro Krampera
Nov 4, 2020·Trends in Molecular Medicine·Tania Martins-MarquesHenrique Girao
Jun 12, 2021·Frontiers in Cell and Developmental Biology·Sadek Munawar, Irene C Turnbull

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Methods Mentioned

BETA
density gradient centrifugation
flow cytometry
protein assay
PMA
fluorescence microscopy
RNAseq
Fluorescence

Software Mentioned

DESeq2
STAR
DESeq2 plotPCA
Kaluza Analysis
Picard
edgeR
Sambamba
AddOrReplaceReadGroups

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