Background@#
Mesenchymal stem cells (MSCs) have been investigated as
therapeutic agents for
inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory
cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and
companion animals. @*Objectives@#This study aimed to assess the
therapeutic effect of
tumor necrosis factor (TNF)-α-stimulated feline
adipose tissue-derived MSCs (fAT-MSCs) in a
dextran sulfate sodium (DSS)-induced
colitis mouse model. @*
Methods@#
Colitis mice was made by
drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the
disease was evaluated and compared.
Raw 264.7 cells were cultured with the
conditioned medium to determine the mechanism, using
quantitative real-time polymerase chain reaction and
enzyme-linked immunosorbent assay. @*Results@#TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced
colitis in
disease activity,
colon length, histologic score, and inflammatory
cytokine. In sectionized
colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b + CD206 +
macrophages than in the other groups.
In vitro, TNF-α-stimulation increased
cyclooxygenase-2 (COX-2) expression and
prostaglandin E2 (
PGE2 )
secretion from fAT-MSCs. The
conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of
interleukin-10 and
arginase-1 in LPS-activated
Raw 264.7 cells. @*Conclusions@#These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed
colon more effectively. Furthermore, we demonstrated that the
effectiveness was interlinked with the COX-2/
PGE2 pathway.