Format

Send to

Choose Destination
Int J Mol Sci. 2019 Apr 2;20(7). pii: E1642. doi: 10.3390/ijms20071642.

Individual Immune-Modulatory Capabilities of MSC-Derived Extracellular Vesicle (EV) Preparations and Recipient-Dependent Responsiveness.

Author information

1
Department of Bone Marrow Transplantation, University Hospital Essen, 45147 Essen, Germany. Lambros.Kordelas@uk-essen.de.
2
Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany. Esther.Schwich@uk-essen.de.
3
Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany. Robin.Dittrich@uk-essen.de.
4
Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany. Peter.Horn@uk-essen.de.
5
Department of Bone Marrow Transplantation, University Hospital Essen, 45147 Essen, Germany. Dietrich.Beelen@uk-essen.de.
6
Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany. Verena.Boerger@uk-essen.de.
7
Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany. Bernd.Giebel@uk-essen.de.
8
Institute for Transfusion Medicine, University Hospital Essen, 45147 Essen, Germany. Vera.Rebmann@uk-essen.de.

Abstract

Treatment with extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been suggested as novel therapeutic option in acute inflammation-associated disorders due to their immune-modulatory capacities. As we have previously observed differences in the cytokine profile of independent MSC-EV preparations, functional differences of MSC-EV preparations have to be considered. To evaluate the immune-modulatory capabilities of specific MSC-EV preparations, reliable assays are required to characterize the functionality of MSC-EV preparations prior to administration to a patient. To this end, we established an in vitro assay evaluating the immune-modulatory capacities of MSC-EV preparations. Here, we compared the efficacy of four independent MSC-EV preparations to modulate the induction of T cell differentiation and cytokine production after phorbol 12-myristate 13-acetate (PMA)/Ionomycin stimulation of peripheral blood mononuclear cells (PBMC) derived from six healthy donors. Flow cytometric analyses revealed that the four MSC-EV preparations differentially modulate the expression of surface markers, such as CD45RA, on CD4+ and CD8+ T cells, resulting in shifts in the frequencies of effector and effector memory T cells. Moreover, cytokine profile in T cell subsets was affected in a MSC-EV-specific manner exclusively in CD8+ naïve T cells. Strikingly, hierarchical clustering revealed that the T cell response towards the MSC-EV preparations largely varied among the different PBMC donors. Thus, besides defining functional activity of MSC-EV preparations, it will be crucial to test whether patients intended for treatment with MSC-EV preparations are in principal competent to respond to the envisioned MSC-EV therapy.

KEYWORDS:

Graft-versus-Host-Disease (GvHD); extracellular vesicles (EV); mesenchymal stem/stromal cells (MSC)

PMID:
30987036
PMCID:
PMC6479947
DOI:
10.3390/ijms20071642
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center