Mesenchymal stem cells improve platelet counts in mice with immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The breakdown of immune tolerance (regulatory T [Treg] cells and suppressor cytokines) plays an important role in ITP pathophysiology, especially in refractory ITP. Bone marrow-derived mesenchymal stem cells (BM-MSCs) show immunomodulatory properties and have been extensively utilized for autoimmune diseases. However, it has not been fully elucidated how BM-MSCs affect ITP. In this study, we explore the therapeutic mechanism of BM-MSCs on ITP in mice.Dose-escalation passive ITP mice were inducted by injection of MWReg30. BALB/c mice were randomly divided into two groups: ITP with BM-MSC transplantation and ITP controls. The serum levels of cytokines (interleukin 10 [IL-10] and transforming growth factor-β1 [TGF-β1]) were examined by enzymelinked immunosorbent assays. The frequency of Treg cells in both peripheral blood and spleen mononuclear cells was analyzed by flow cytometry, and the forkhead box P3 (Foxp3) messenger RNA (mRNA) level was measured by realtime polymerase chain reaction. After BM-MSC treatment, the platelet (PLT) counts were significantly elevated. Meanwhile, cytokines (TGF-β1 and IL-10), the ratios of Treg cells, and the Foxp3 mRNA expression level were significantly higher in the BM-MSC group. Our results show that BM-MSCs can improve PLT counts mainly by secreting suppressive cytokines and upregulating Tregs, which may provide new therapeutic potential for human ITP. K E Y W O R D Sbone marrow-derived mesenchymal stem cells, forkhead box P3, interleukin 10, immune thrombocytopenia, transforming growth factor-β1, regulatory T cells

Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles

“…Treatments with MSCs + TAT NP and MSCs + TAT PTX NP resulted in about 30% to 60% increase in platelet count (Table 2). Previous studies have shown that MSCs can increase platelet count through induction of interlukein-10 (IL-10) and TGF-β [36]. None of the other hematological parameters were affected by the treatments (Table 2, Table S1).…”

The Mechanistic Effects and Clinical Applications of Various Derived Mesenchymal Stem Cells in Immune Thrombocytopenia

“…ITP-MSCs cannot proliferate routinely and are defective in immunomodulation. Exogenous BM-MSCs have been shown to reverse this defect of proliferation and immunomodulation in both in vitro cytological experiments and in vivo animal experiments [32,33]. Substantial differences exist between BM-MSCs and BM-MSCs in ITP (ITP-MSCs) in terms of their appearance, proliferation, apoptosis, senescence, and differentiation (Table 2) [14,34,35].…”

miRNA-98-5p Targeting IGF2BP1 Induces Mesenchymal Stem Cell Apoptosis by Modulating PI3K/Akt and p53 in Immune Thrombocytopenia

“…MSCs have been demonstrated to be beneficial for ITP mice. 15 To better understand the role of miR-98-5p in MSCs during ITP, we established an active ITP model and injected ITP mice with miR-98-5pmodified MSCs to observe the resultant therapeutic effects. One week after transferring immunized splenocytes, platelet counts significantly decreased in ITP mice (Figure 5A), and there was obvious bleeding in subcutaneous tissues, abdomen, lungs, and intestines.…”

“…11 Based on the ability to modulate immune responses, MSCs have been used in the treatment of various inflammatory diseases, such as steroid-resistant acute graft-versus-host disease, cardiovascular disease, and autoimmune disorders. [12][13][14] In particular, MSCs have been reported to be efficacious in improving platelet levels in ITP mice, 15,16 and the intravenous infusion of umbilical cord-derived MSCs seems to be effective in refractory ITP patients. 17 Given the promising therapeutic effects of MSCs in ITP and the key roles of MSCs during ITP development and progression, it is necessary to investigate the precise molecular signals that lead to MSC dysfunction in ITP.…”