A new parallel plate flow chamber that has a linear variation of shear stress, starting from a predetermined maximum value at the entrance and falling to zero at the exit, has been designed and tested. This is in contrast to the usual rectangular channel plan which produces a constant shear stress over the entire length. The new design is based on the theory of Hele-Shaw flow between parallel plates. To verify the efficacy of the flow channel, the effect of fluid shear stress on platelet adhesion to a fibrinogen-coated glass surface was tested. The percentage of attached platelets after 5 min of shear stress is shown to be a function of shear stress. With this new flow chamber, cell-cell interactions can be studied efficiently over a wide range of shear stress using a single run at constant discharge.
Mesenchymal stem/stromal cells (MSCs) are promising potential candidates for the treatment of immunological diseases because of their immunosuppressive functions. However, the molecular mechanisms that mediate MSCs’ immunosuppressive activity remain elusive. In this article, we report for the first time, to our knowledge, that secreted growth-regulated oncogene (GRO) chemokines, specifically GRO-γ, in human MSC-conditioned media have an effect on the differentiation and the function of human monocyte-derived dendritic cells. The monocyte-derived dendritic cells were driven toward a myeloid-derived suppressor cell (MDSC)–like phenotype by the GRO chemokines. GRO-γ–treated MDSCs had a tolerogenic phenotype that was characterized by an increase in the secretion of IL-10 and IL-4, and a reduction in the production of IL-12 and IFN-γ. We have also shown that the mRNA expression levels of the arginase-1 and inducible NO synthase genes, which characterize MDSCs, were upregulated by GRO-γ–primed mouse bone marrow cells. In addition, the ability of GRO-γ–treated bone marrow–derived dendritic cells to stimulate the OVA-specific CD8+ T (OT-1) cell proliferation and the cytokine production of IFN-γ and TNF-α were significantly decreased in vivo. Our findings allow a greater understanding of how MDSCs can be generated and offer new perspectives to exploit the potential of MDSCs for alternative approaches to treat chronic inflammation and autoimmunity, as well as for the prevention of transplant rejection.
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