title: Sca1(+) mesenchymal stromal cells inhibit graft-versus-host disease in mice after bone marrow transplantation.
abstract: Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several subpopulations, which have not been individually assessed for their role in GVHD suppression. In this study, we assessed the immunosuppressive effect of bone-related Sca1(+) MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic hematopoietic stem cell transplantation (HCT). Our results showed that Sca1(+) MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival period of allogeneic HCT recipients. This effect was exerted through lowered T lymphocyte infiltration in target organs and by inhibition of CD80/86 expression on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the recipient splenocytes. In conclusion, bone-related Sca1(+) MSCs subpopulation suppressed GVHD and could be a novel treatment for acute GVHD.
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wen
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Yaozhen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinic Molecular Research Center, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Yue
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: An
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xin
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, 710032, China.
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Daping Hospital, the Third Military Medical University, 400042, China. Electronic address: buyi.chu@gmail.com.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Transfusion Medicine, Xijing Hospital, the Fourth Military Medical University, 710032, China. Electronic address: hxbyqh@fmmu.edu.cn.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D000067696:Ataxin-1 / Q000276:immunology*; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016019:Survival Analysis
chemical_list: D000067696:Ataxin-1; C000593750:Atxn1 protein, mouse
keywords: Acute GVHD; Bone marrow transplantation; CTLA-4; Co-stimulatory molecule; Mesenchymal stem cell