title: CXCR4-transduced mesenchymal stem cells protect mice against graft-versus-host disease.
abstract: Mesenchymal stem cells (MSCs) possessing immunoregulatory activities have been evaluated in the treatment of graft-versus-host disease (GVHD). However, the immunomodulatory effects of MSCs are not always successfully achieved in some animal models, and this deficiency may be caused in part by poor homing of these cells to hematopoietic tissues. In this study, we assessed the immunsuppressive capacity of lentiviral vector transduced MSCs expressing CXCR4 in a major histocompatibility complex (MHC)-mismatched mouse model of bone marrow (BM) transplantation from C57BL/6 donors to BALB/c recipients. 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 interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17A were also determined using a Cytometric Bead Array. CXCR4 over-expressing MSCs maintained their immunsuppressive capacity and showed enhanced migration capacity in vitro. In the mouse GVHD model, treatment with CXCR4 over-expressing MSCs decreased the mortality rate and attenuated clinical and pathological GVHD scores. Moreover, compared with control groups, the plasma IL-2, IL-6, IFN-γ and TNF-α levels in recipients infused with CXCR4 over-expressing MSCs were significantly decreased, while those of IL-4 and IL-10 were increased. In conclusion, our report reveals that CXCR4-transduced MSCs effectively controlled the occurrence of mouse GVHD following allogeneic BM transplantation.
authors.affiliation: Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Hanzhong Road, Nanjing, Jiangsu Province 210029, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yan
authors.forename: Hai
authors.initials: H
authors.lastname: Cheng
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002633:Chemotaxis / Q000235:genetics; D016207:Cytokines / Q000097:blood; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D007165:Immunosuppression Therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D019718:Receptors, CXCR4