An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles
The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs) is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs) exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lac...
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doaj-70d198c2c01b4d808c5daa80ce5707f92020-11-24T21:23:14ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-07-01187141310.3390/ijms18071413ijms18071413An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular VesiclesKarin Pachler0Nina Ketterl1Alexandre Desgeorges2Zsuzsanna A. Dunai3Sandra Laner-Plamberger4Doris Streif5Dirk Strunk6Eva Rohde7Mario Gimona8GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaInstitute of Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaGMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaGMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaUniversity Clinic for Blood Group Serology and Transfusion Medicine, Paracelsus Medical University (PMU), Lindhofstrasse 20, 5020 Salzburg, AustriaGMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaInstitute of Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaGMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaGMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, AustriaThe regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs) is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs) exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies.https://www.mdpi.com/1422-0067/18/7/1413extracellular vesiclesexosomesT-cell proliferationimmune modulationmesenchymal stromal cellsmesenchymal stem/progenitor cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karin Pachler Nina Ketterl Alexandre Desgeorges Zsuzsanna A. Dunai Sandra Laner-Plamberger Doris Streif Dirk Strunk Eva Rohde Mario Gimona |
spellingShingle |
Karin Pachler Nina Ketterl Alexandre Desgeorges Zsuzsanna A. Dunai Sandra Laner-Plamberger Doris Streif Dirk Strunk Eva Rohde Mario Gimona An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles International Journal of Molecular Sciences extracellular vesicles exosomes T-cell proliferation immune modulation mesenchymal stromal cells mesenchymal stem/progenitor cells |
author_facet |
Karin Pachler Nina Ketterl Alexandre Desgeorges Zsuzsanna A. Dunai Sandra Laner-Plamberger Doris Streif Dirk Strunk Eva Rohde Mario Gimona |
author_sort |
Karin Pachler |
title |
An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles |
title_short |
An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles |
title_full |
An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles |
title_fullStr |
An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles |
title_full_unstemmed |
An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles |
title_sort |
in vitro potency assay for monitoring the immunomodulatory potential of stromal cell-derived extracellular vesicles |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-07-01 |
description |
The regenerative and immunomodulatory activity of mesenchymal stromal cells (MSCs) is partially mediated by secreted vesicular factors. Extracellular vesicles (EVs) exocytosed by MSCs are gaining increased attention as prospective non-cellular therapeutics for a variety of diseases. However, the lack of suitable in vitro assays to monitor the therapeutic potential of EVs currently restricts their application in clinical studies. We have evaluated a dual in vitro immunomodulation potency assay that reproducibly reports the inhibitory effect of MSCs on induced T-cell proliferation and the alloantigen-driven mixed leukocyte reaction of pooled peripheral blood mononuclear cells in a dose-dependent manner. Phytohemagglutinin-stimulated T-cell proliferation was inhibited by MSC-derived EVs in a dose-dependent manner comparable to MSCs. In contrast, inhibition of alloantigen-driven mixed leukocyte reaction was only observed for MSCs, but not for EVs. Our results support the application of a cell-based in vitro potency assay for reproducibly determining the immunomodulatory potential of EVs. Validation of this assay can help establish reliable release criteria for EVs for future clinical studies. |
topic |
extracellular vesicles exosomes T-cell proliferation immune modulation mesenchymal stromal cells mesenchymal stem/progenitor cells |
url |
https://www.mdpi.com/1422-0067/18/7/1413 |
work_keys_str_mv |
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