Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages

• DOI: 10.1038/s41598-017-09827-5
• Publication Date: 2017-08-21T08:06:01Z
• Authors: Ji-young Song; Hyo Jeong Kang; Joon Seok Hong; Chong Jai Kim; Jae-Yoon Shim; Christopher W. Lee; Jene Choi
• Keywords: 0303 health sciences; Science; Macrophages; Q; Dextran Sulfate; R; Cell Differentiation; Mesenchymal Stem Cells; Macrophage Activation; Colitis; Mesenchymal Stem Cell Transplantation; Article; Umbilical Cord; 3. Good health; Intestines; Mice, Inbred C57BL; 03 medical and health sciences; Medicine; Animals; Cytokines; Humans; Caco-2 Cells

AbstractHuman 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.