title: In patients with chronic aplastic anemia, bone marrow-derived MSCs regulate the Treg/Th17 balance by influencing the Notch/RBP-J/FOXP3/RORγt pathway.
abstract: The standard treatment for aplastic anemia (AA) in young patients is a matched sibling hematopoietic stem cell transplant. Transfusion of a chronic AA patient with allogeneic bone marrow-derived mesenchymal stromal cells (BMMSCs) is currently being developed as a cell-based therapy, and the safety and efficacy of such transfusions are being continuously improved. Nevertheless, the mechanisms by which BMMSCs exert their therapeutic effects remain to be elucidated. In this study, mesenchymal stromal cells (MSCs) obtained from bone marrow donors were concentrated and intravenously injected into 15 chronic AA patients who had been refractory to prior immunosuppressive therapy. We showed that BMMSCs modulate the levels of Th1, Th2, Th17 and Treg cells, as well as their related cytokines in chronic AA patients. Furthermore, the percentages of Th1 and Th17 cells among the H-MSCs decreased significantly, while the percentage Treg cells increased. The Notch/RBP-J/FOXP3/RORγt pathway was involved in modulating the Treg/Th17 balance after MSCs were transfused in vitro. Additionally, the role played by transfused MSCs in regulating the Treg/Th17 balance via the Notch/RBP-J/FOXP3/RORγt pathway was further confirmed in an AA mouse model. In summary, in humans with chronic AA, BMMSCs regulate the Treg/Th17 balance by affecting the Notch/RBP-J/FOXP3/RORγt pathway.
authors.affiliation: Department of Hematology, General Hospital of Guangzhou Military Command of Chinese PLA; Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Guangzhou University of Chinese Medicine; Guangzhou, Guangdong 510405, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, General Hospital of Guangzhou Military Command of Chinese PLA; Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Hematology, General Hospital of Guangzhou Military Command of Chinese PLA; Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Zujun
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Hematology, General Hospital of Guangzhou Military Command of Chinese PLA; Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Zenghui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Hematology, General Hospital of Guangzhou Military Command of Chinese PLA; Guangzhou, Guangdong 510010, P.R. China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong, 510000, P.R. China.
authors.forename: Haijia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong, 510000, P.R. China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405 P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lan
authors.affiliation: Department of Hematology, General Hospital of Guangzhou Military Command of Chinese PLA; Guangzhou, Guangdong 510010, P.R. China.|Guangdong Saliai Stem Cell Research Institute, Guangzhou, Guangdong, 510000, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C497570:RBPJ protein, human; D051880:Receptors, Notch