Clinical Potential of MSC-EVs and Translational Challenges
Bernd Giebel,
Group Leader, Institute for Transfusion Medicine,
University Hospital Duisburg-Essen
Small (exosome-sized) extracellular vesicles (sEVs) harvested from supernatants of human mesenchymal stromal cells (MSCs) exert therapeutic functions in various disease models. Furthermore, they have been successfully applied in a steroid-refractory Graft-versus-Host Disease patient and in a single centre, randomized, placebo-controlled phase II/III clinical pilot study on chronic kidney disease patients without revealing any site effects. Apparently one mode of action is their ability to modulate immune responses from the pro-inflammatory into the regulatory state. At the example of an ischemic stroke model, we demonstrate that systemically applied MSC-sEV preparations, considered as therapeutically active, attenuate stroke induced lymphopenia and neutrophil immigration into the lesion site and thus importantly contribute to the MSC-sEVs’ therapeutic effect. Notably, independent MSC-sEV preparations can differ in their immunomodulatory and therapeutic activity, with a proportion of them appearing therapeutically inactive. Thus, according to our understanding it is a challenging but essential task during the translation process into the clinics to develop appropriate potency assays allowing discrimination of therapeutically active and therapeutically inactive MSC-sEV preparations.
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