Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.
24 June 2021 in IEEE Transactions on Biomedical Engineering
Objective: Laparoscopic renal denervation (LRDN) ablates sympathetic nerves on the outer wall of a renal artery to treat autonomic nervous system disorders such as hypertension and arrhythmia. Here, we developed a new circular radio frequency (RF) electrode for LRDN using micro-electro-mechanical systems (MEMS) technology. Methods: The electrode consists of a parallel bipolar MEMS electrode, two MEMS thermocouples, and a shape-memory alloy (SMA) substrate. The electrode is automatically wrapped and unwrapped under actuation controlled by the heat generated by RF energy on the electrodetissue interface. The electrode was designed through a computational simulation analysis, and its actuation and temperature-sensing performance were tested in laboratory experiments and a porcine animal study. Results: In an in-vivo study of porcine renal arteries, the electrode could automatically wrap and unwrap around an artery during LRDN. The bipolar MEMS electrode required 13 Vrms for heat generation up to 60 C, while the two MEMS thermocouples reliably measured the temperature without noise signals (a temperature coefficient of 38.3 or 38.5 V/C and an accuracy of 0.44 or 0.49 C). As revealed in a histological analysis using hematoxylin and eosin staining and Massons trichrome staining, the renal artery was intact after LRDN. Conclusion: The circular RF electrode improves the safety of LRDN by reliably measuring the electrode temperature of the electrode during RDN and enhances the effectiveness of LRDN by reducing the complicated manipulations of the surgical instrument. Significance: The developed circular RF electrode will pave the way for LRDN treatment of autonomic nervous system disorders.
Methane, a greenhouse gas with 21 times the global warming potential of carbon dioxide, is increasingly subject to stringent emission regulations, driving the demand for high-performance methane sensors. This study proposes a novel IR spectroscopy technique based on a CuBDC-integrated microcantilever (CuBDC-microcantilever IR spectroscopy) for CH4 sensing, offering exceptional sensitivity and selectivity. The metal-organic framework (MOF) CuBDC was synthesized on the microcantilever using a drop-and-dry method facilitated by an intense pulsed light technique. Characterization via scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy confirmed the successful formation of CuBDC on the microcantilever. The CuBDC-microcantilever IR spectroscopy demonstrated a significantly enhanced sensitivity, with a differential amplitude at the CH4 characteristic peak approximately 13 times higher than that of a conventional Si microcantilever. Moreover, the limit of detection was determined to be as low as 14.05 ppm. The clear separation of the CH4 characteristic peak from the water and acetone vapor peaks also emphasized the sensor’s high selectivity. These findings highlight the superior sensitivity and selectivity of the proposed sensor, positioning it as a promising platform for CH4 detection in industrial and environmental applications.
Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to have a therapeutic effect on nephrotoxicity. As animal models require significant time and resources to evaluate drug effects, there is a need for a new experimental technique that can accurately predict drug effects in humans. We evaluated the therapeutic effect of MSC-derived EVs in cisplatin nephrotoxicity using a three-dimensional, gravity-driven, two-layer tubule-on-a-chip (3D-MOTIVE chip). In the 3D-MOTIVE chip, 10 μM cisplatin decreased the number of attached cells compared to the vehicle. Conversely, annexin V and reactive oxygen species (ROS) were increased. Cell viability was increased 2.8-fold and 2.5-fold after treatment with EVs at 4 and 8 µg/mL, respectively, compared to the cisplatin-induced nephrotoxicity group. Cell attachment was increased 2.25-fold by treatment with 4 µg/mL EVs and 2.02-fold by 8 µg/mL EVs. Annexin V and ROS levels were decreased compared to those in the cisplatin-induced nephrotoxicity group. There were no significant differences in annexin V and ROS levels according to EV concentration. In sum, we created a cisplatin-induced nephrotoxicity model on a 3D-MOTIVE chip and found that MSC-derived EVs could restore cell viability. Thus, MSC-derived EVs may have the potential to ameliorate cisplatin-induced nephrotoxicity.
26 April 2021 in Journal of Inclusion Phenomena and Macrocyclic Chemistry