Transplanting of Adipose Derived Stem Cells Up-Regulate CD4+CD25+Foxp3+ T Cells in a Murine Model of Passive Chronic Immune Thrombocytopenia

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder in which antibodies and/or T cells lead to enhanced peripheral platelet destruction and reduced bone marrow platelet production. The dysregulated CD4+CD25+Foxp3+ T regulatory cells (Tregs) play a critical role in the pathophysiology of ITP. Human adipose-derived mesenchymal stem cells (hADSCs) were recently found to suppress effector T cell responses and to have beneficial effects in various immune disorders. However, it is not clear how ADSCs could affect ITP. This study is aimed to investigate the therapeutic effect of ADSCs on the treatment of ITP mice and explore the underlying mechanisms. Methods: A passive immune thrombocytopenia animal model was induced by injection of the monoclonal antiplatelet antibody MWReg30, and ADSC injection was performed on the 2nd day after ITP induction. PLT counts have been measured by an automatic blood cell counter daily after ADSC transplant for 6 days. The frequency of Tregs in the blood was analyzed by flow cytometry. mRNAs and proteins of Foxp3, TGF-β1 and IL-10 in the spleen, thymus and lymph nodes were detected by RT-PCR and western blotting respectively. Findings: Transplant of ADSCs on ITP mice led to increased PLT counts, an up-regulation of Tregs in the blood, and an up-regulation of Foxp3, TGF-β1 and IL-10 mRNA and protein in the spleen, thymus and lymph nodes as compared with the untreated ITP mice. Conclusion: ADSCs transplant may be an available method in therapy of ITP. ADSCs transplant may affect proliferation and function of Tregs in ITP, and Foxp3, TGF-β1 and IL-10 may be involved in this process. Funding: This work was supported by the Youth Program of National Natural Science Founds (8150091), The Doctoral Start Project of Natural Science Foundation of Guangdong Province(2015A030310022) and the Youth Program of Natural Science Founds of Hunan Province (2018JJ3472). Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: All experimental procedures conformed to the Guidelines of Animal Experiments from the Chinese Committee of Medical Ethics and were approved by the Commission of Animal Research, Sun Yat-sen University Medical Center. Raw human aspirates from patients undergoing lipectomy were collected after obtaining informed consent according to procedures approved by the Ethics Committee of the Chinese Academy of Medical Sciences and the First Affiliated Hospital of South China University.