| Abstract [eng] |
Acute inflammation is associated with many neurodegenerative diseases. In central nervous system inflammatory process is regulated by resident tissue macrophages, named microglia. In physiology conditions microglial cells are ramified, but during neuroinflammation microglia become activated. During microglial activation cell morphology is changed either to M1, the typically activated phenotype, or to M2, an alternatively activated phenotype. The aim of this study is to investigate the exosomes effect on the activation of human microglial cells. Exosomes were obtained from the stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs). During this study effective in vitro polarization of human microglial cells into M1 and M2 states was established. In addition, potential targets of exosomes in human microglial cells were identified. Obtained results indicate that exosomes affect expression of genes involved in the regulation of inflammatory response (ARG1, iNOS, VEGFA), phagocytosis (CD11b, TREM2) and also unspecific immune response (CD14, TLR4). Moreover, exosomes significantly affected expression of miR-124-3p and miR-145-5p in M0, M1 and M2 microglial cells. Another important finding of this study was that exosomes activate migration and phagocytic activity of human microglial cells. In conclusion, it demonstrates that exosomes derived from SHEDs can act as potent immunomodulators of human microglial cells. Herein, successful implementation of this project provides knowledge about neuroprotective and anti-inflammatory properties of exosomes which might be helpful for the development of new therapeutic strategies against neurodegenerative disorders. Structure: introduction, literature review, materials and methods, results and discussion, conclusions and references. Thesis consist of: 50 p. text without appendixes, 14 pictures, 4 table, 79 bibliographical entries. |
