Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice. (8th June 2018)

• Record Type: Journal Article
• Authors: Zheng, Xiao-Bin; He, Xiao-Wen; Zhang, Long-Juan; Qin, Hua-Bo; Lin, Xu-Tao; Liu, Xuan-Hui; Zhou, Chi; Liu, Hua-Shan; Hu, Tuo; Cheng, Hai-Chun; He, Xiao-Sheng; Wu, Xian-Rui; Chen, Yu-Feng; Ke, Jia; Wu, Xiao-Jian; Lan, Ping
• Is Part Of: Gastroenterology report. Volume 7:Number 2(2019)
• Page Start: 127
• Page End: 138
• Publication Date: 2018-06-08
• Subjects: Inflammatory bowel disease -- tumorigenesis -- mesenchymal stem cells -- CXCR4 -- mice; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1093/gastro/goy017
• Languages: English
• ISSNs: 2052-0034

Abstract

Abstract: Background and Objective: Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells (MSCs) for the treatment of inflammatory bowel disease (IBD) and IBD-induced cancer. However, whether MSCs have the ability to suppress or promote tumor development remains controversial. The stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis is well known to play a critical role in the homing of MSCs. In this study, we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD. Methods: MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein (GFP). Chemotaxis and invasion assays were used to detect CXCR4 expression. A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium (DSS). The mice were divided into three groups and then injected with phosphate buffer saline (PBS), MSC-GFP or MSC-CXCR4. Results: Compared with the mice injected with MSC-GFP, the mice injected with MSC-CXCR4 showed relieved weight loss, longer colons, lower tumor numbers and decreased tumor load; expression of pro-inflammatory cytokines decreased, and signal transducer and activator of transcription 3 (STAT3) phosphorylation level in colon tissue was down-regulated. Conclusion: CXCR4-overexpressing MSCs exhibited effective anti-tumor function, which may be associated with enhanced homing to inflamed intestinal tissues.