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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

【摘要】:正Human umbilical cord blood derived stromal cells (hUCBDSCs),a novel resource isolated from CD34+ cells by our laboratory,have been previously shown not only to be nonimmunogenic but also to exert an immunosuppressive effect on xenogenic T cells in vitro. 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 which hUCBDSCs regulate acute GVHD(aGVHD) in haploidentical stem cell transplantation in mice.Expression of VLA-4 was explored by flow cytometry in spleen lymphocytes of donor mice cocultured with hUCBDSCs and in haploidentical stem cell transplantation in mice with aGVHD.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(p0.05). Cotransplantation of bone marrow with hUCBDSCs significantly decreased the expression of VLA-4 compared with control mice(p0.05).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.

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