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Bernd Giebel Institute for Transfusion Medicine, Germany |
Abstract
Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Up to now, more than 800 NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases, including graft-versus-host disease (GvHD) and ischemic stroke. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs seem to exert their beneficial effects rather in a paracrine manner than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, are discussed to execute the MSCs’ therapeutic effects. Indeed, we observed beneficial therapeutic impacts of MSC-EVs in a patient, who suffered from steroid-refractory acute GvHD. Furthermore, beneficial effects were observed in animal models for several different diseases. According to controversial reports in the MSC field, especially since a phase III clinical trial failed to show clinical efficacy in MSC treated GvHD patients, we have started to compare immunomodulatory effects of independent MSC-EV preparations. Indeed, in our in vitro assays independent MSC-EV fractions reveal different immunomodulatory capabilities. To unravel the basis for these differences we are currently using several methods to dissect the heterogeneity between and within given MSC-EV samples.
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