Abstract
Endometrial regenerative cells (ERCs) are a new type of mesenchymal-like stromal cells, and their therapeutic potential has been tested in a variety of disease models. SDF-1/CXCR4 axis plays a chemotaxis role in stem/stromal cell migration. The aim of the present study was to investigate the role of SDF-1/CXCR4 axis in the immunomodulation of ERCs on the experimental colitis. The immunomodulation of ERCs in the presence or absence of pretreatment of SDF-1 or AMD3100 was examined in both in vitro cell culture system and dextran sulphate sodium-induced colitis in mice. The results showed that SDF-1 increased the expression of CXCR4 on the surface of ERCs. As compared with normal ERCs, the SDF-1-treated, CXCR4 high-expressing ERCs more significantly suppressed dendritic cell population as well as stimulated both type 2 macrophages and regulatory T cells in vitro and in vivo. Meanwhile, SDF-1-pretreated ERCs increased the generation of anti-inflammatory factors (e.g., IL-4, IL-10) and decreased the pro-inflammatory factors (e.g., IL-6, TNF-α). In addition, SDF-1-pretreated CM-Dil-labeled ERCs were found to engraft to injured colon. Our results may suggest that an SDF-1-induced high level of CXCR4 expression enhances the immunomodulation of ERCs in alleviating experimental colitis in mice.
Highlights
Inflammatory bowel disease (IBD) is a chronic disabling inflammatory process that includes ulcerative colitis (UC) and Crohn’s disease (CD), and its damage mainly involves in the ileum, colon, and rectum [1]
C-X-C chemokine receptor type 4 (CXCR4) high-expressing Endometrial regenerative cells (ERCs) suppressed the generation of dendritic cells (DCs) and promoted of Type 2 macrophage (M2) and Regulatory T cells (Tregs) in vitro The effects of CXCR4 expression of ERCs on the generations of DCs (CD11c+ MHCII+), M2 (CD68+ CD206+), and Tregs
CXCR4 high-expressing ERCs alleviated dextran sulphate sodium (DSS)-induced experimental colitis In the untreated group, we found that the body weight of the mice decreased significantly during the first 5 days, as alleviated the Disease Activity Index (DAI) of DSS-induced colitis in mice. c, d Mice were sacrificed at day 10 after DSS induction
Summary
Inflammatory bowel disease (IBD) is a chronic disabling inflammatory process that includes ulcerative colitis (UC) and Crohn’s disease (CD), and its damage mainly involves in the ileum, colon, and rectum [1]. Li et al Stem Cell Research & Therapy (2019) 10:204 regenerative cells, which could both come into a therapeutic effect and overcome the shortcomings of MSCs. Endometrial regenerative cells (ERCs) are mesenchymallike stromal cells, which can be isolated from human menstrual blood [12]. We and others have demonstrated that ERCs are excellent candidates for the treatment of numerous experimental disease models, such as prevention or attention of renal ischemiareperfusion injury [17], acute liver injury [18], and critical limb ischemia [16] in mouse models. Our group has demonstrated that ERCs could attenuate experimental colitis in mice by regulating T and B cell responses [19, 20], as well as by reducing the infiltration of inflammatory cells to the damaged tissues [19]. The indepth mechanisms of ERCs in the treatment of colitis are not well understood, which may be required for further development of ERCs as a novel cell therapy to alleviate colitis in patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
