CD73 activity of mesenchymal stromal cell-derived extracellular vesicle preparations is detergent-resistant and does not correlate with immunomodulatory capabilities

• DOI: 10.1016/j.jcyt.2022.09.006
• Publication Date: 2022-10-14T11:34:48Z
• Authors: Fabiola Nardi Bauer; Tobias Tertel; Oumaima Stambouli; Chen Wang; Robin Dittrich; Simon Staubach; Verena Börger; Dirk M. Hermann; Sven Brandau; Bernd Giebel
• Keywords: Extracellular Vesicles; Extracellular vesicles

Background aimsExtracellular vesicles (EVs) derived from human mesenchymal stromal cells (MSCs) show immunomodulatory activity in different assays both vitro and vivo. In previous work, the authors compared potential of independent MSC-EV preparations a multi-donor mixed lymphocyte reaction (mdMLR) assay an optimized steroid-refractory acute graft-versus-host disease (aGVHD) mouse model. The observed that only proportion showed capabilities demonstrated with mdMLR immunomodulating activities were able to suppress aGVHD symptoms vivo vice versa. Since is complex depends on primary donors, sought establish much easier standardize fulfills requirements for becoming qualified as potency assay.MethodsThe bona fide MSC antigen CD73 possesses ecto-5'-nucleotidase cleaves pro-inflammatory extracellular adenosine monophosphate into anti-inflammatory free phosphate. To test whether reflected their potential, adopted enzymatic monitors quantitative manner well-characterized containing or lacking activity.ResultsThe did not correlate ability modulate T-cell responses thus improving symptomatology Furthermore, was resistant EV-destroying detergent treatment.ConclusionsEcto-5'-nucleotidase neither reflects authors' nor provides any information about integrity respective EVs. Thus, enzyme indicative products. development appropriate products remains challenging.Graphical abstract