Abstract
Mesenchymal stem cells (MSCs) produce immunomodulatory factors that regulate production of cytokines and chemokines in immune cells affecting their functional properties. Administration of MSCs-sourced secretome, including MSC-derived conditioned medium (MSC-CM) and MSC-derived exosomes (MSC-Exos), showed beneficial effects similar to those observed after transplantation of MSCs. Due to their nano-size dimension, MSC-Exos easily penetrate through the tissue and in paracrine and endocrine manner, may deliver MSC-sourced factors to the target immune cells modulating their function. MSCs derived from amniotic fluid (AF-MSCs) had superior cell biological properties than MSCs derived from bone marrow. We recently developed “Exosomes Derived Multiple Allogeneic Proteins Paracrine Signaling (Exo-d-MAPPS)”, a biological product in which the activity is based on AF-MSC-derived Exos capable to deliver immunomodulatory molecules and growth factors to the target cells. Herewith, we analyzed immunosuppressive capacity of Exo-d-MAPPS against human peripheral blood mononuclear cells (pbMNCs) and demonstrated that Exo-d-MAPPS efficiently suppressed generation of inflammatory phenotype in activated pbMNCs. Exo-d-MAPPS attenuated production of inflammatory cytokines and promoted generation of immunosuppressive phenotype in Lipopolysaccharide-primed pbMNCs. Exo-d-MAPPS treatment reduced expansion of inflammatory Th1 and Th17 cells and promoted generation of immunosuppressive T regulatory cells in the population of Concanavalin A-primed pbMNCs. Similarly, Exod-MAPPS treatment suppressed pro-inflammatory and promoted anti-inflammatory properties of α-GalCer-primed pbMNCs.
In summing up, due to its capacity for suppression of activated pbMNCs, Exo-d-MAPPS should be further explored in animal models of acute and chronic inflammatory diseases as a poten-tially new remedy for the attenuation of detrimental immune response.
Use of four-colour flow cytometry to evaluate conjugate formation between human peripheral blood mononuclear cells and tumour target cells