title: Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients.
abstract: Human umbilical cord matrix/Wharton's jelly (hUC)-derived mesenchymal stem cells (MSC) have been shown to have marked therapeutic effects in a number of inflammatory diseases and autoimmune diseases in humans based on their potential for immunosuppression and their low immunogenicity. Currently, no data are available on the effectiveness of UC-MSC transplantation in immune thrombocytopenia (ITP) patients. It was the objective of this study to assess the effect of allogeneic UC-MSCs on ITP patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BM-MNCs) from ITP patients and healthy controls were co-cultured with UC-MSCs for three days and seven days, respectively. Flow cytometry and ELISA were applied to assess the various parameters. In PBMCs from ITP patients, the proliferation of autoreactive T, B lymphocytes and destruction of autologous platelets were dramatically suppressed by UC-MSCs. UC-MSCs not only suppressed co-stimulatory molecules CD80, CD40L and FasL expression but also in shifting Th1/Th2/Treg cytokines profile in ITP patients. UC-MSCs obviously reversed the dysfunctions of megakaryocytes by promoting platelet production and decreasing the number of living megakaryocytes as well as early apoptosis. In addition, the level of thrombopoietin was increased significantly. Our clinical study showed that UC-MSCs play a role in alleviating refractory ITP by increasing platelet numbers. These findings suggested that UC-MSCs transplantation might be a potential therapy for ITP.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People’s Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Zeping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Donglei
authors.initials: D
authors.lastname: Zhang
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Yang
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yang
authors.forename: Renchi
authors.initials: R
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001323:Autoantibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D002681:China; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000276:immunology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology / Q000601:surgery*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D034061:Thrombopoiesis; D013997:Time Factors; D014470:Umbilical Cord / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D059631:Wharton Jelly / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators