title: Regulation of acute graft-versus-host disease by human umbilical cord blood derived stromal cells in haploidentical stem cell transplantation in mice through very late activation antigen-4.
abstract: Human umbilical cord blood derived stromal cells (hUCBDSCs), a novel resource isolated by our laboratory, have been shown to exert an immunologic regulation. Very late activation antigen-4 (VLA-4) has been associated with graft-versus-host disease (GVHD). This study aimed to investigate the possible mechanism by in vitro co-cultured splenocytes of donor mice with hUCBDSCs and in haploidentical stem cell transplantation in mice with acute GVHD. Both hUCBDSCs and human bone marrow stromal cells (hBMSCs) elicited decreased lymphocyte expression of VLA-4, but this decrease was stronger with hUCBDSCs than with hBMSCs (p<0.05). Cotransplantation of bone marrow with hUCBDSCs significantly decreased the expression of VLA-4 compared with control mice (p<0.05). A significant reduction of VLA-4 labeling in the target organs of GVHD was evident in haploidentical mice cotransplanted with hUCBDSCs. Our study shows that hUCBDSCs may protect mouse recipients of haploidentical stem cell transplantation from aGVHD via downregulating the expression of VLA-4.
authors.affiliation: Department of Hematology, Xinqiao Hospital, the Third Military Medical University, Chongqing, People's Republic of China. chzhang2003@tom.com
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Pei-Yan
authors.initials: PY
authors.lastname: Kong
authors.forename: Xian-Gui
authors.initials: XG
authors.lastname: Peng
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Sun
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000166:cytology; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000502:physiology*
chemical_list: D039041:Integrin alpha4beta1