Exo-D-Mapps Attenuates Production of Inflammatory Cytokines and Promoted Generation of Immunosuppressive Phenotype in Peripheral Blood Mononuclear Cells

Serbian Journal of Experimental and Clinical Research

卷:23

Fellabaum Crissy¹  Harrell Carl Randall¹  Acovic Aleksandar²  Miloradovic Dragana³  Volarevic Vladislav⁴  Arsenijevic Nebojsa⁴  Markovic Bojana Simovic⁴  Miloradovic Dragica⁴ 

[1] Regenerative Processing Plant, LLC, Palm Harbor, Florida, United States of America;

[2] University of Kragujevac, Faculty of Medical Sciences, Department of Dentistry, Kragujevac, Serbia;

[3] University of Kragujevac, Faculty of Medical Sciences, Department of Genetics, Kragujevac, Serbia;

[4] University of Kragujevac, Faculty of Medical Sciences, Department of Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, Kragujevac, Serbia;

关键词: mesenchymal stem cells;    amniotic fluid;    secretome;    immunosuppression;    mononuclear cells;   

DOI  :  10.2478/sjecr-2019-0045

来源: DOAJ

【 摘 要 】

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 potentially new remedy for the attenuation of detrimental immune response.

【 授权许可】

Unknown