Mesenchymal stem cells-derived extracellular vesicles containing miR-378a-3p inhibit the occurrence of inflammatory bowel disease by targeting GATA2.

This study sought to determine whether mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) carrying microRNA-378a-3p (miR-378a-3p) could affect the pathogenesis of inflammatory bowel disease (IBD) by regulating the GATA-binding protein 2 (GATA2)/aquaporin-4 (AQP4)/peroxisome proliferator-activated receptor α (PPAR-α) axis. Initially, colon mucosa biopsy tissues were harvested from healthy controls and patients with IBD for qRT-PCR and immunohistochemistry analysis. EVs harvested from MSCs and lipopolysaccharide (LPS) were used to stimulate the M064 cells to establish an in vitro inflammation cell model. Besides, 2,4,6-trinitrobenzene sulfonic acid intracolon administration was performed to establish in vivo IBD mouse models. After loss- and gain-of-function assays, the regulatory role of MSCs-derived EVs loaded with manipulated miR-378a-3p in IBD in relation to GATA2/AQP4/PPAR-α were explored. Upregulation of GATA2 was identified in the colon tissue of IBD patients. GATA2, which was a target gene of miR-378a-3p, transcriptionally upregulated AQP4. After silencing of GATA2, LPS-induced apoptosis of M064 cells was reduced by the downregulation of AQP4. Decreased AQP4 contributed to PPAR-α pathway inactivation and weakened the LPS-induced apoptosis of M064 cells. MSCs-EVs delivering miR-378a-3p suppressed the GATA2/AQP4/PPAR-α pathway, which reduced LPS-induced apoptosis of M064 cells and the occurrence of IBD in mice. Altogether, the current study illustrated that MSCs-EVs transfer miR-378a-3p to reduce the GATA2 expression, which downregulates AQP4 to block the PPAR-α signalling pathway, thus suppressing the occurrence of IBD.

High efficiency integration of three-dimensional functional microdevices inside a microfluidic chip by using femtosecond laser multifoci parallel microfabrication.

High efficiency fabrication and integration of three-dimension (3D) functional devices in Lab-on-a-chip systems are crucial for microfluidic applications. Here, a spatial light modulator (SLM)-based multifoci parallel femtosecond laser scanning technology was proposed to integrate microstructures inside a given 'Y' shape microchannel. The key novelty of our approach lies on rapidly integrating 3D microdevices inside a microchip for the first time, which significantly reduces the fabrication time. The high quality integration of various 2D-3D microstructures was ensured by quantitatively optimizing the experimental conditions including prebaking time, laser power and developing time. To verify the designable and versatile capability of this method for integrating functional 3D microdevices in microchannel, a series of microfilters with adjustable pore sizes from 12.2 µm to 6.7 µm were fabricated to demonstrate selective filtering of the polystyrene (PS) particles and cancer cells with different sizes. The filter can be cleaned by reversing the flow and reused for many times. This technology will advance the fabrication technique of 3D integrated microfluidic and optofluidic chips.