SDF-1/CXCR4 axis enhances the immunomodulation of human endometrial regenerative cells in alleviating experimental colitis.

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.

• Authors: Xiang Li, Xu Lan, Yiming Zhao, Grace Wang, Ganggang Shi, Hongyue Li, Yonghao Hu, Xiaoxi Xu, Baoren Zhang, Kui Ye, Xiangying Gu, Caigan Du, Hao Wang
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 10 Issue 1 Pg. 204 (07 08 2019) ISSN: 1757-6512 [Electronic] England
• PMID: 31286993 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzylamines
• CXCR4 protein, human
• Chemokine CXCL12
• Cyclams
• Heterocyclic Compounds
• Receptors, CXCR4
• plerixafor

Topics

• Animals
• Benzylamines
• Cells, Cultured
• Chemokine CXCL12 (pharmacology, therapeutic use)
• Colitis (chemically induced, drug therapy, metabolism)
• Cyclams
• Endometrium (cytology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Heterocyclic Compounds (pharmacology, therapeutic use)
• Humans
• Male
• Mice, Inbred BALB C
• Receptors, CXCR4 (metabolism)
• Spleen (cytology)
• T-Lymphocytes, Regulatory (drug effects, metabolism)