title: Over-expression of CXCR4 on mesenchymal stem cells protect against experimental colitis via immunomodulatory functions in impaired tissue.
abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) are attractive candidates for tissue regeneration and immunoregulation in inflammatory bowel disease. However, their in vivo reparative capability is limited owing to barren efficiency of BMSCs to injury region. Stromal cell-derived factor (SDF-1) plays an important role in chemotaxis and stem cell homing through interaction with its specific receptor CXC chemokine receptor 4 (CXCR4). The present study was designed to investigate the role of SDF-1α/CXCR4 axis in the therapeutic effects of lentivirus-preconditioned BMSCs for 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis rats. BMSCs were isolated from female Sprague-Dawley rats and identified by flow cytometry. Lentiviral transduction was applied to over-express CXCR4/GFP (Ad-CXCR4-BMSCs) or null/GFP (Ad-GFP-BMSCs). Efficacy of engraftment was determined by the presence of enhanced green fluorescent protein (GFP) positive cells. One week after intravenous administration, Ad-GFP-BMSCs failed to colonize in the inflamed colon and had no beneficial effect in TNBS-induced colitis. Instead, Ad-CXCR4-BMSCs signally ameliorated both clinical and microanatomical severity of colitis. Immunofluorescence and western blotting showed that Ad-CXCR4-BMSCs migrated toward inflamed colon was more efficient than Ad-GFP-BMSCs. The therapeutic effect of Ad-CXCR4-BMSCs was mediated by the suppression of pro-inflammatory cytokines and STAT3 phosphorylation in injured colon. Collectively, our data indicated that over-expression CXCR4 led to enhance in vivo mobilization and engraftment of BMSCs into inflamed colon where these cells can function as an anti-inflammatory and immunomodulatory component of the immune system in TNBS-induced colitis.
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Liu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zuo
authors.forename: Heng
authors.initials: H
authors.lastname: Fan
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.forename: Zhexing
authors.initials: Z
authors.lastname: Shou
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zou
mesh_terms: D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D003106:Colon / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D056747:Immunomodulation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014302:Trinitrobenzenesulfonic Acid