title: Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression.
abstract: : Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-α markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP)IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP.
  
  
  
  Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types and promotes mesenchymal stem cell (MSC) proliferation. PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.|Collaborative Innovation Center of Hematology, Peking University, Beijing, People's Republic of China.
authors.forename: Jia-Min
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Fei-Er
authors.initials: FE
authors.lastname: Feng
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Qian-Ming
authors.initials: QM
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Fu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.|Collaborative Innovation Center of Hematology, Peking University, Beijing, People's Republic of China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.|Collaborative Innovation Center of Hematology, Peking University, Beijing, People's Republic of China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China zhangxh100@sina.com xjhrm@medmail.com.cn.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.|Collaborative Innovation Center of Hematology, Peking University, Beijing, People's Republic of China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China zhangxh100@sina.com xjhrm@medmail.com.cn.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.|Collaborative Innovation Center of Hematology, Peking University, Beijing, People's Republic of China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000077214:Becaplermin; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects*; D006801:Humans; D007165:Immunosuppression Therapy; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000473:pathology*; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000906:Antibodies; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D020574:Proto-Oncogene Proteins c-sis; D053218:Receptors, Death Domain; D016159:Tumor Suppressor Protein p53; D000077214:Becaplermin
keywords: Apoptosis; Immunosuppression; Mesenchymal stem cells; Platelet-derived growth factor-BB; Senescence