An In Vitro Potency Assay for Monitoring the Immunomodulatory Potential of Stromal Cell-Derived Extracellular Vesicles.

Karin Pachler, Nina Ketterl, Alexandre Desgeorges, Zsuzsanna A Dunai, Sandra Laner-Plamberger, Doris Streif, Dirk Strunk, Eva Rohde, Mario Gimona

Journal: International journal of molecular sciences 2018;18(7):1413

PMID: 28671586

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Abstract

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.

Address: GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Institute of Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; University Clinic for Blood Group Serology and Transfusion Medicine, Paracelsus Medical University (PMU), Lindhofstrasse 20, 5020 Salzburg, Austria. [email protected].; GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Institute of Experimental and Clinical Cell Therapy, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; University Clinic for Blood Group Serology and Transfusion Medicine, Paracelsus Medical University (PMU), Lindhofstrasse 20, 5020 Salzburg, Austria. [email protected].; GMP Unit, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; Research Program Nanovesicular Therapies, Paracelsus Medical University (PMU), Strubergasse 22, 5020 Salzburg, Austria. [email protected].; University Clinic for Blood Group Serology and Transfusion Medicine, Paracelsus Medical University (PMU), Lindhofstrasse 20, 5020 Salzburg, Austria. [email protected].

DOI: 10.3390/ijms18071413

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MeSH Terms: Cell-Derived Microparticles, Cells, Cultured, Exosomes, Extracellular Vesicles, Humans, Immunomodulation, Isoantigens, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Mesenchymal Stem Cells, Stromal Cells, T-Lymphocytes