Abstract

Therapeutic Potentials of Mesenchymal Stem Cell-derived Extracellular Vesicles

Bernd Giebel, Group Leader, Institute for Transfusion Medicine, University Hospital Duisburg-Essen

More than 500 NIH registered clinical trials applied MSCs to treat a variety of different diseases such as myocardial infarction, stroke and graft-versus-host disease (GvHD). Initially, MSCs were thought to replace lost cells in damaged tissues. Despite contrary reports regarding the outcome of MSC treatments, MSCs seem to exert their beneficial effects by the secretion of immunosuppressive factors and/or small extracellular vesicles (EVs, 70-150 nm), such as exosomes and microvesicles, rather than by interacting into affected tissues. After setting up techniques for the characterization and large scale preparation of EVs, we have treated a steroid-refractory GvHD patient with EVs/exosomes enriched from MSC supernatants (MSC-EVs) (Kordelas et al., 2014). In addition we investigate the MSC-EVs’ therapeutic potential to exert neuroprotective functions in animal models for ischemic stroke and preterm brain injury. So fare, we observed beneficial effects in all settings. In the murine stroke model we performed a side by side comparison of the therapeutic effect of MSCs and their EVs and did not recognize any differences, both improved the symptoms significantly (Doeppner et al., 2015). At the functional level MSC-EVs were shown to exert immunosuppressive functions in vivo and in vitro. In addition, they seem to promote pro-regenerative processes. Due to the contrary reports regarding the outcome of MSC treatments and the fact that MSCs are a very heterogeneous, ill-defined class of fibroblastic cells with adipogenic, cartilogenic and osteogenic differentiation potentials, we consider that not all human MSCs release therapeutic effective EVs. To this end, we harvested EVs from cell-culture supernatants of different donor-derived MSCs and analyzed their immunomodulatory properties on human T cells. Indeed, differences were observed in the MSC-EVs’ capabilities to suppress T cell functions. Currently, we are improving the platform to produces MSC-EVs for the clinical set