Organoids derived from self‐organizing stem cells represent a major technological breakthrough with the potential to revolutionize biomedical research. However, building high‐fidelity organoids in a reproducible and high‐throughput manner remains challenging. Here, a droplet microfluidic system is developed for controllable fabrication of hybrid hydrogel capsules, which allows for massive 3D culture and formation of functional and uniform islet organoids derived from human‐induced pluripotent stem cells (hiPSCs). In this all‐in‐water microfluidic system, an array of droplets is utilized as templates for one‐step fabrication of binary capsules relying on interfacial complexation of oppositely charged Na‐alginate (NaA) and chitosan (CS). The produced hybrid capsules exhibit high uniformity, and are biocompatible, stable, and permeable. The established system enables capsule production, 3D culture, and self‐organizing formation of human islet organoids in a continuous process by encapsulating pancreatic endocrine cells from hiPSCs. The generated islet organoids contain islet‐specific α‐ and β‐like cells with high expression of pancreatic hormone specific genes and proteins. Moreover, they exhibit sensitive glucose‐stimulated insulin secretion function, demonstrating the capability of these binary capsules to engineer human organoids from hiPSCs. The proposed system is scalable, easy‐to‐operate, and stable, which can offer a robust platform for advancing human organoids research and translational applications.
COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.
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