PMID- 28842625 OWN - NLM STAT- MEDLINE DCOM- 20190604 LR - 20190604 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Aug 25 TI - Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages. PG - 9412 LID - 10.1038/s41598-017-09827-5 [doi] LID - 9412 AB - Human umbilical cord mesenchymal stem cells (hUC-MSCs), originating in Wharton's jelly, are multipotent stem cells that home to damaged tissues and can modulate the immune system. We examined whether administering extracts of MSCs (MSC-Ex) instead of MSCs could augment the beneficial effects of MSC therapy by overcoming the low homing efficiency of MSCs systemically administered in inflammatory bowel diseases (IBD). Dextran sodium sulfate-induced colitis model was established in C57BL/6 mice, and MSC-Ex was administered intraperitoneally. MSC-Ex reduced colitis, disease activity index (DAI), and histological colitis scores, and increased the body weight. Treatment with MSC-Ex completely blocked the induction of inflammatory cytokines, which were strongly detected in mice with colitis. MSC-Ex shifted the macrophage functional phenotype from M1 to M2 by decreasing the levels of MCP1, CXCL9, and iNOS, but increasing the levels of IL-10, LIGHT, CCL1, and Arg-1. MSC-Ex recovered the destruction of the epithelial barrier in the differentiated Caco-2 cells in vitro. Treatment with MSC-Ex was more potent than that with MSC in reducing DAI, the histological score, and nitrite levels. These data strongly support that MSC-Ex treatment can be a potent approach to overcome severe refractory IBD. FAU - Song, Ji-Young AU - Song JY AD - Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. FAU - Kang, Hyo Jeong AU - Kang HJ AD - Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. AD - Department of Physiology, Asan-Minnesota Institute for Innovating Transplantation, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. FAU - Hong, Joon Seok AU - Hong JS AD - Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Gyeonggi-do, Korea. FAU - Kim, Chong Jai AU - Kim CJ AD - Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. FAU - Shim, Jae-Yoon AU - Shim JY AD - Department Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. FAU - Lee, Christopher W AU - Lee CW AD - Department of Molecular and Cellular Biology, University of California, Davis, Davis, California, USA. FAU - Choi, Jene AU - Choi J AD - Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. jenec@amc.seoul.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170825 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Cytokines) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - Caco-2 Cells MH - Cell Differentiation MH - Colitis/*chemically induced/pathology/*therapy MH - Cytokines/metabolism MH - Dextran Sulfate/toxicity MH - Humans MH - Intestines/cytology MH - *Macrophage Activation MH - Macrophages/physiology MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/cytology MH - Mice, Inbred C57BL MH - Umbilical Cord PMC - PMC5573412 COIS- The authors declare that they have no competing interests. EDAT- 2017/08/27 06:00 MHDA- 2019/06/05 06:00 PMCR- 2017/08/25 CRDT- 2017/08/27 06:00 PHST- 2017/05/02 00:00 [received] PHST- 2017/07/31 00:00 [accepted] PHST- 2017/08/27 06:00 [entrez] PHST- 2017/08/27 06:00 [pubmed] PHST- 2019/06/05 06:00 [medline] PHST- 2017/08/25 00:00 [pmc-release] AID - 10.1038/s41598-017-09827-5 [pii] AID - 9827 [pii] AID - 10.1038/s41598-017-09827-5 [doi] PST - epublish SO - Sci Rep. 2017 Aug 25;7(1):9412. doi: 10.1038/s41598-017-09827-5.