o:1571 Efekti mezenhimalnih matičnih ćelija u mišjem modelu akutnog zapaljenja debelog creva izazvanog dekstran natrijum sulfatom Effects of mesenchymal stem cells in mouse model of acute dextran sodium sulphate-induced colitis : doctoral dissertation sr Mezenhimalne matične ćelije (engl. Mesenchymal stem cells-MSC) imaju terapeutski potencijal u mnogim stanjima, uključujući gastrointestinalnim bolestima. Njihov efekat na supresiju patogene uloge dendritskih ćelija (engl. dendritic cells-DC) u oštećenju debelog creva nije otkriven. U ovom istraživanju su po prvi put opisani efekti MSC na DC u kolitisu izazvanim dekstran natrijum sulfatom, koji predstavlja dobar model za istraživanje ulceroznog kolitisa. Dva miliona MSC su intraperitonealno aplikovane dnevno podeljenih u tri dnevnih doza. Ocenjivanje znaka razvoja bolesti, analiziranje ćelija imunskog sistema koje su infiltisale lamina propriadebelog creva i produkcije sistemskih citokina je korišćeno za procenu efekata MSC. Dodatno je sprovedena deplecija makrofaga i pasivni transfer in vivo stimulisanih DC, kao i kultivisanje MSC i DC, određivanje produkcije citokina i promene fenotipa DC. Aplikovane MSC su pozitivno uticale na smanjenje razvoja kolitisa. Aplikacije su značajno smanjile progresiju bolesti, smanjile produkciju sistemskih proinflamacijskih citokina (IL-1β, IL-12 i IL-6) i redukovale procentualnu zastupljenost infiltrisanih proinflamacijskih ćelija imunskog sistema u lamina propria. Njihov pozitivan efekat na ublažavanje znakova kolitisa je bio evidentan čak i nakon deplecije makrofaga. Pasivni transfer in vivo MSC stimulisanih DC ublažio je ozbiljnost kolitisa. MSC parakrinim načinom, produkcijom Galektina 3 smanjile su produkciju proinflamacijskih citokina (TNFα, IL-1β, IL-12 i IL-6) u DC i umanjile ekspresiju CD86, CD80 i I-A molekula na njihovoj membrani uključenih u prezentaciji antigena. Sve zajedno, ovi rezultati ukazuju da aplikovane MSC pozitivne efekte na smanjenje kolitisa izazvanog dekstran natrijum sulfatom postižu supresijom DC. Mesenchymal stem cells (MSC) have therapeutic potential in many conditions, including gastrointestinal diseases. Their effect on suppression of pathogenic role of dendritic cells (DC) in colon injury is not revealed. Here, for the first time is described the effects of MSC on dendritic cells in dextran sodium sulfate (DSS)-induced colitis, used as a well-established model of ulcerative colitis. Divided in three doses, two million MSC were intraperitoneally administered daily. Assessing signs of disease development, analysis of infiltrated of immune cells in colon lamina propria and production of systemic cytokines were used to evaluate effects of MSC. Additionally, depletion of macrophages and passive transfer of in vivo primed DC was performed, as well as co-culture of DC and MSC, measurement of cytokines production and phenotype changing of DC. Administered MSC positively affects the decreased development of colitis. The administration of MSC significantly reduced progression of disease, decreased the production of systemic proinflammatory cytokines (IL-1β, IL-12, and IL-6), and reduced percentage of infiltrated proinflammatory immune cells in lamina propria. Their effect was evident even after depletion of macrophages. Passive transfer of in vivo MSC-primed DC reduced severity of colitis. MSC in paracrine manner, by increased production of Galectin 3, down-regulated the production of proinflammatory cytokines (TNFα, IL-1β, IL-12, and IL-6) in DC, and attenuated expression of CD86, CD80 and I-A, molecules on their membranes involved in antigen presentation. Taken together, these results indicate that applied MSC achieve positiveeffects on attenuation of DSS-induced colitis by suppressing DC. - 91552100 108180745 91552101 8612 2023-02-13T11:51:50.053Z 45 no 46 Aleksandar Z., 1986- Nikolić 96610569 2018 63 mentor Miodrag, 1964- Stojković 13591655 2018 63 član komisije Vladislav, 1979- Volarević 10776423 2018 63 član komisije Biljana, 1974- Ljujić 5345383 2018 63 član komisije Diana, 1956- Bugarski 1665383 2018 97 listova 5355422 http://phaidrakg.kg.ac.rs/o:1571 no yes 13 2023-02-13T11:51:50.320Z 70 mezenhimalne matične ćelije, kolitis izazvan dekstran natrijum sulfatom, dendritske ćelije mesenchymal stem cells, dss-induced colitis, dendritic cells 577.27:616-08(043.3) 1738 34A05 2018