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Acquired forms of Aplastic anemia (AA) are characterized by T cell‐mediated immune disease resulting in bone marrow (BM) failure and marrow hypoplasia. In these cases, it is a major challenge to modulate autoreactive T cell activity and thereby decrease the pro‐inflammatory cytokine storm. Emerging evidence indicates that extracellular vesicles derived from mesenchymal stem cells (MSC‐EVs) control and modulate immunity. The therapeutic potential of MSC‐EVs has not been investigated in acquired AA. Hence, in this study, we constructed an AA mice model through irradiation and splenocyte infusion to test the benefits of hypoxic MSC‐EVs (Hx‐EVs) and normoxic MSC‐EVs (Nx‐EVs). We found that MSC‐EVs treatment significantly prolonged the survival rate and increased the platelet (PLT) counts of the AA mice. Immunohistochemical staining and colony assay confirmed amelioration of hypoplasia in the BM and increased numbers of hematopoietic stem cells (HSCs). These effects of MSC‐EVs were mediated by T cell suppression and inhibition of interferon‐gamma (IFN‐γ) and tumor necrosis factor‐alpha (TNF‐α) production in the AA mouse model. In addition, an in vitro study revealed that MSC‐EVs led to reduced IFN‐γ and TNF‐α levels and there was an association with decreased splenocyte viability. Previous studies examined the diagnostic and prognostic values of microRNAs (miRNAs) in AA and identified miR‐199a, miR‐146a, miR‐223, and miR‐126. We used quantitative real‐time PCR to evaluate the expression of these miRNAs on isolated BM mononuclear cells (BM‐MNCs) from treated and untreated AA mice. miR‐223, miR‐146a, and miR‐199a expressions increased in the MSC‐EVs treated AA mice. Treatment with MSC‐EVs increased expression of miR‐223 and miR‐146a. Our findings showed that treatment with MSC‐EVs significantly ameliorated immune destruction of HSCs in the AA mouse model and confirmed the importance of miRNAs in the clinical status of this model.

Background Leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. There are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. We explained here that K562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of human primary cord blood-derived T cells (CB T cells). Methods Human primary cord blood-derived T cells were treated with K562-derived exosomes. We evaluated the expression variation of some critical genes activated in suppressor T cells. The alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using ELISA assay and real-time PCR. Finally, NO production and intracellular ROS level in CB T cells were evaluated using Greiss assay and flow cytometry, respectively. Results Our results showed the over-expression of the genes involved in inhibitory T cells, including NQO1, PD1, and FoxP3. In contrast, genes involved in T cell activation such as CD3d and NFATc3 have been reduced significantly. Also, the expression of interleukin 10 (IL-10) and interleukin 6 (IL-6) mRNAs were significantly up-regulated in these cells upon exosome treatment. In addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (IL-17) proteins increased in T cells exposed to K562-derived exosomes. Finally, K562-derived exosomes induce significant changes in the NO production and intracellular ROS levels in CB T cells. Conclusions These results demonstrate that K562-derived exosomes stimulate the immunosuppressive properties in CB-derived T cells by inducing anti-inflammatory cytokines such as IL-10, reducting ROS levels, and arising of NO synthesis in these cells. Moreover, considering the elevation of FOXP3, IL-6, and IL-17 levels in these cells, exosomes secreted by CML cells may induce the fates of T cells toward tumor favorable T cells instead of conventional activated T cells.

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Aim: Human bone marrow mesenchymal stem cells (hBMSCs) may be infected by parvovirus B19 (B19V). hBMSCs support bone marrow hematopoiesis by producing stromal cells, secretion of cytokines and growth factors, etc. Because of the lifetime persistent infection of the virus in healthy individual’s bone marrow, this study aims to evaluate B19V effects on hBMSCs gene expression of some crucial hematopoietic cytokines. Materials & methods: hBMSCs were transfected with pHI0 plasmid containing the B19V genome. The quantitative mRNA expression of target genes was evaluated 24 h after transfection. Results: Our findings demonstrated a significant increase in expression levels of IL-11 and TPO (p < 0.05). Conclusion: We concluded that alteration in the gene expressions in B19V-infected hBMSCs might have significant effects on the bone marrow microenvironment as well as hematopoiesis.