P072 - MESENCHYMAL STEM CELLS AMELIORATE DSS-INDUCED CHRONIC COLITIS IN MICE BY INDUCING PHENOTYPIC CHANGES OF DENDRITIC CELLS.
(Room Poster Hall)
19 Jan 18
5:30 PM
-
7:00 PM
Tracks:
Clinical and Research Challenges
Background/Aim: Mesenchymal stem cells (MSCs), which are an emerging cell therapeutic for inflammatory bowel disease (IBD), have demonstrated immunomodulatory effects through interactions with T cells and dendritic cells (DCs). Methods: In this study, we investigated whether MSCs could induce the differentiation of mature DCs (mDCs) into regulatory DCs. We also investigated whether MSC-DCs (imDCs co-cultured with MSCs) could alleviate inflammation through T cell modulation in a dextran sulfate sodium (DSS)-induced chronic colitis mouse model. Results: Splenocytes co-cultured with MSC-DCs resulted in the elevated expression of regulatory T (Treg) cell markers in vitro. MSC-DCs expressed CD11c+ CD80low CD86low cell surface markers. These MSC-DCs also secreted high levels of anti-inflammatory cytokines, whereas production of pro-inflammatory cytokines was diminished in vitro. The levels of FOXP3, CD4 and CD25 were increased in splenocytes co-cultured with MSC-DCs. Furthermore, intraperitoneal injection of MSC-DCs significantly increased anti-inflammatory cytokines and enhanced differentiation of FOXP3+ Treg cells in vivo, resulting in considerable amelioration of chronic colitis and improvement of survival rates in DSS-treated mice. Conclusion: These results showed that MSC-DCs ameliorated chronic colitis by promoting both Treg cell differentiation and the secretion of anti-inflammatory cytokines, providing evidence that supports the potential application of MSC-DCs in the treatment of IBD.