No abstract

The COVID‐19 pandemic has continued to spread rapidly, and patients with diabetes are at risk of experiencing rapid progression and poor prognosis for appropriate treatment. Continuous glucose monitoring (CGM), which includes accurately tracking fluctuations in glucose levels without raising the risk of coronavirus exposure, becomes an important strategy for the self‐management of diabetes during this pandemic, efficiently contributing to the diabetes care and the fight against COVID‐19. Despite being less accurate than direct blood glucose monitoring, wearable noninvasive systems can encourage patient adherence by guaranteeing reliable results through high correlation between blood glucose levels and glucose concentrations in various other biofluids. This review highlights the trending technologies of glucose sensors during the ongoing COVID‐19 pandemic (2019–2020) that have been developed to make a significant contribution to effective management of diabetes and prevention of coronavirus spread, from off‐body systems to wearable on‐body CGM devices, including nanostructure and sensor performance in various biofluids. The advantages and disadvantages of various human biofluids for use in glucose sensors are also discussed. Furthermore, the challenges faced by wearable CGM sensors with respect to personalized healthcare during and after the pandemic are deliberated to emphasize the potential future directions of CGM devices for diabetes management.

Regulatory macrophages (Mreg) are a special cell type that present a potential therapeutic strategy for various inflammatory diseases. In vitro, Mreg generation mainly takes 7–10 days of treatment with chemicals, including cytokines. In the present study, we established a new approach for Mreg generation using a three-dimensional (3D) micropatterned polydimethylsiloxane (PDMS) surface coated with a natural biopolymer adhesive polydopamine (PDA) and the common cell adhesion peptide motif arginylglycylaspartic acid (RGD). The 3D PDMS surfaces were fabricated by photolithography and soft lithography techniques and were subsequently coated with an RGD+PDA mixture to form a surface that facilitates cell adhesion. Human monocytes (THP-1 cells) were cultured on different types of 2D or 3D micropatterns for four days, and the cell morphology, elongation, and Mreg marker expression were assessed using microscopic and flow cytometric analyses. The cells grown on the PDA+RGD-coated 3D micropatterns (20-µm width/20-µm space) exhibited the most elongated morphology and strongest expression levels of Mreg markers, such as CD163, CD206, CD209, CD274, MER-TK, TREM2, and DHRS9. The present study demonstrated that PDA+RGD-coated 3D PDMS micropatterns successfully induced Mreg-like cells from THP-1 cells within four days without the use of cytokines, suggesting a time- and cost-effective method to generate Mreg-like cells in vitro.

Regulatory macrophages (Mregs) are unique in that they have anti-inflammatory and immunosuppressive properties. Thus, treating inflammatory diseases using Mregs is an area of active research. Human Mregs are usually generated by culturing peripheral blood monocytes stimulated using a macrophage colony-stimulating factor with interferon (IFN)-γ. Herein, we generated Mregs with an elongated cell morphology from THP-1 cells that were stimulated with phorbol 12-myristate 13-acetate and cultured with both arginylglycylaspartic acid and vitamin D3. These Mregs regulated macrophage function, and respectively downregulated and upregulated the expression of pro-inflammatory and immunosuppressive mediators. They also expressed Mregs-specific markers, such as dehydrogenase/reductase 9, even when exposed to such inflammatory stimulants as IFN-γ, lipopolysaccharide, purified xenogeneic antigen, and xenogeneic cells. The Mregs also exerted anti-inflammatory and anticoagulatory actions in response to xenogeneic cells, as well as exerting immunosuppressive effects on mitogen-induced Jurkat T-cell proliferation. Our method of generating functional Mregs in vitro without cytokines is simple and cost-effective.

The outstanding role of regulatory macrophages (Mregs) in promoting immunomodulation allowed the clinical application of Mregs-based therapies for controlling unwanted immune responses, especially in the field of transplantation. The major obstacle known to prevent pig-to-human xenotransplantation is the interaction between the human natural anti-Gal antibody and the -Gal epitope (Gal1-3Gal1-4GlcNAc-R). A promising strategy to eliminate the interaction between human immune cells and porcine transplanted organs is to generate Mregs, which is tolerant to -Gal epitope. We established a protocol to generate and characterize Mregs from human monocytes THP-1 cells, specifically resistant to porcine antigen -Gal. The cells were stimulated with a series of stimulants including GM-CSF, IFN-, dexamethasone, vitamin D3, and porcine-specific antigen -Gal. The generated Mregs displayed fiber-like morphology and high levels of CD16, CD163, CD206, Mer-TK, DHRS9, increased mitochondrial fusion and induced histone H3 lysine 4 monomethylation (H2K27me1). Importantly, Mregs showed suppressed inflammatory mediators gene expression and decreased tissue factor-coagulation signaling under co-culture with pig endothelial cells. Our results illustrate a feasible approach for generating functional Mregs which would be an effective and safe tool for pig-to-human xenotransplantation.