Therapeutic Potential of “Exosomes Derived Multiple Allogeneic Proteins Paracrine Signaling: Exosomes d-MAPPS” is Based on the Effects of Exosomes, Immunosuppressive and Trophic Factors

摘要

Due to their differentiation capacity and potent immunosuppressive and pro-angiogenic properties, mesenchymal stem cells (MSCs) have been considered as new therapeutic agents in regenerative medicine. Since most of MSC-mediated beneficent effects are a consequence of their paracrine action, we designed MSC-based product “Exosomes Derived Multiple Allogeneic Proteins Paracrine Signaling (Exosomes d-MAPPS), which activity is based on MSCs-derived growth factors and immunomodulatory cytokines capable to attenuate inflammation and to promote regeneration of injured tissues. Interleukin 1 receptor antagonist (IL-1Ra) and IL-27 were found in high concentrations in Exosomes d-MAPPS samples indicating strong anti-inflammatory and immunosuppressive potential of Exosomes d-MAPPS. Additionally, high concentrations of vascular endothelial growth factor receptor (VEGFR1) and chemokines (CXCL16, CCL21, CXCL14) were noticed at Exosomes d-MAPPS samples suggesting their potential to promote generation of new blood vessels and migration of CXCR6, CCR7 and CXCR4 expressing cells. Since all proteins which were found in high concentration in Exosomes d-MAPPS samples (IL-1Ra, CXCL16, CXCL14, CCL21, IL-27 and VEGFR1) are involved in modulation of lung, eye, and synovial inflammation, Exosomes d-MAPPS samples were prepared as inhalation and ophthalmic solutions in addition to injection formulations; their application in several patients suffering from chronic obstructive pulmonary disease, osteoarthritis, and dry eye syndrome resulted with significant improvement of biochemical and functional parameters. In conclusion, Exosomes d-MAPPS, due to the presence of important anti-inflammatory, immunomodulatory, and pro-angiogenic factors, represents potentially new therapeutic agent in regenerative medicine that should be further tested in large clinical studies.