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
Author
Nikolić, Aleksandar Z.Mentor
Stojković, MiodragCommittee members
Volarević, VladislavLjujić, Biljana
Bugarski, Diana
Metadata
Show full item recordAbstract
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 propria
debelog 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
zna...čajno 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 progressi...on 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 positive
effects on attenuation of DSS-induced colitis by suppressing DC.