title: Protective effects of mesenchymal stem cells with CXCR4 up-regulation in a rat renal transplantation model.
abstract: The homing of mesenchymal stem cells to injured tissue, which is important for the correction of conditions such as ischemia-reperfusion injury (IRI) and immunolesions, has been performed previously, but with poor efficiency. Substantial improvements in engraftment are required to derive clinical benefits from MSC transplantation. Chemokines are the most important factors that control cellular migration. Stromal derived factor-1 (SDF-1) is up-regulated during tissue/organ ischemia damage, and its cognate receptor, chemokine receptor 4 (CXCR4), is involved in stem cell migration. The aim of our study was to investigate CXCR4 expression in MSCs and to validate both its role in mediating migration to transplanted kidneys and its immunoregulatory effects in renal protection. Specifically, the present study was designed to investigate the short-term tissue homing of MSCs carrying genetically modified CXCR4 in a rat renal transplantation model. We tested the hypothesis that MSCs with CXCR4 over-expression can more efficiently regulate immunological reactions. Lentiviral vectors were used to over-express CXCR4 or to introduce a short hairpin ribonucleic acid (shRNA) construct targeting endogenous CXCR4 in rat MSCs. MSCs were labeled with enhanced green fluorescent protein (eGFP). After cell sorting, recipient kidneys were regionally perfused; recipient animals were injected with transduced MSCs, native MSCs, or PBS via tail vein following renal transplantation; and the effects of MSC injection were observed.
authors.affiliation: Department of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fuli
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hongbao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Liaoning Province Translational Medicine Laboratory, Department of Urinary Urology and Cardiology of General Hospital of Shenyang Military Region, Shenyang, China.
authors.forename: Long
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China ; Liaoning Province Translational Medicine Laboratory, Department of Urinary Urology and Cardiology of General Hospital of Shenyang Military Region, Shenyang, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D006084:Graft Rejection / Q000517:prevention & control*; D049452:Green Fluorescent Proteins / Q000032:analysis; D016030:Kidney Transplantation; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D019737:Transplants / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins