title: [Effect of lentiviral vector mediated CXCR4 gene overexpressed mesenchymal stem cell on the protection of mice against graft-versus-host disease].
abstract: OBJECTIVE
  To investigate the effect of the lentiviral vector mediated CXCR4 overexpressed mesenchymal stem cell (MSCs) on graft-versus-host disease (GVHD).
  
  
  METHODS
  Lentiviral vector containing CXCR4 was constructed. CXCR4 overexpressed MSC by lentiviral vector mediated were assessed. A major histocompatibility complex (MHC)-mismatched mouse model of bone marrow transplantation (BMT) from C57BL/6 donors to BALB/c recipients was constructed. Mice were divided into five groups: total body irradiation (TBI) group, mice received irradiation only; BMT group, mice were transplanted with bone marrow (BM) after TBI; GVHD group, mice were transplanted with BM and splencytes after TBI; CXCR4-MSC group, mice were transplanted with CXCR4-MSC, BM and splencytes after TBI; EGFP-MSC group, mice were transplanted with EGFP-MSC, BM and splencytes after TBI. The survival, body weight and clinical score of GVHD in transplanted mice were monitored. Liver, intestine and skin from mice in each group were obtained for histological examination. Plasma concentrations of inflammation factors such as interleukin (IL)-2, IFN-γ and TNF-α were also determined using a cytometric bead array cytokine kit.
  
  
  RESULTS
  All mice in TBI group died within 14 days, while all of BMT group survived. The mean survival times for GVHD, EGFP-MSC and CXCR4-MSC groups were (17.0 ± 2.3) d, (21.7 ± 4.8) d and (30.1 ± 9.1) d, respectively. Treatment with CXCR4 over-expressing MSCs could decrease the mortality rate. All mice in each group developed clinical signs such as hunched posture, dull fur, diarrhea and weight loss. Meanwhile, histopathological findings in target organs were confirmed the presence of GVHD. While, clinical GVHD scores and histopathological scores in CXCR4-MSC group were significantly lower than that of GVHD group. Moreover, compared with control groups, the plasma IL-2, IFN-γ and TNF-α level in recipients infused with CXCR4-MSC were significantly decreased (P<0.05).
  
  
  CONCLUSIONS
  The results revealed that CXCR4- transduced MSCs could effectively control the occurrence of mouse GVHD following allogeneic BM transplantation.
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D016207:Cytokines; D005822:Genetic Vectors / Q000235:genetics; D006086:Graft vs Host Disease; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D019718:Receptors, CXCR4