No abstract

Organ-on-a-chip platforms serve as cost-efficient testbeds for screening pharmaceutical agents, mimicking natural physiology, and studying disease. In the field of diabetes, the development of an islet-on-a-chip platform would have broad implications in understanding disease pathology and discovering potential therapies. Islet microphysiological systems are limited, however, by their poor cell survival and function in culture. A key factor that has been implicated in this decline is the disruption of islet-matrix interactions following isolation. Herein, we sought to recapitulate the in vivo peri-islet niche using decellularized extracellular matrix (ECM) hydrogels. Sourcing from porcine bladder, lung, and pancreas tissues, 3-D ECM hydrogels were generated, characterized, and validated using both rodent and human pancreatic islets. Optimized decellularization protocols resulted in hydrogels with distinctive viscoelastic properties that correlated to their matrix composition. The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid. These supportive 3-D physiomimetic ECM hydrogels can be leveraged within microfluidic platforms for the long-term culture of islets.

Gastric cancer (GC) is one of the most common malignancies worldwide. To the best of our knowledge, no biomarkers have been widely accepted for the early diagnosis and prognostic prediction of GC. This study aimed to identify potential novel prognostic biomarkers for GC. The dataset GSE29272, which originates from the public database Gene Expression Omnibus, was employed in the present study. The online tool GEO2R was used to calculate the differentially expressed genes (DEGs) in GSE29272 between tumour tissues and adjacent tissues. CytoHubba and MCODE plugins of Cytoscape software were used to obtain hub genes and modules of DEGs. The online tools Database for Annotation, Visualisation and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes were employed to conduct Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and to construct protein-protein interaction networks. A total of 117 DEGs were extracted from GSE29272. In addition, 15 hub genes and seven modules were identified in the 117 DEGs. The enrichment analysis revealed that they were mainly enriched in GO biological process and cellular component domains, and the ‘ECM-receptor interaction’, ‘focal adhesion’, ‘metabolism of xenobiotics by cytochrome P450’ and ‘drug metabolism’ pathways. The hub genes asporin ( ASPN ), collagen type I α1 chain ( COL1A1 ), fibronectin 1 ( FN1 ), versican ( VCAN ) and mucin 5AC ( MUC5AC ) were demonstrated to have prognostic value for patients with GC. The ASPN and VCAN genes were significantly associated with overall survival and disease-free survival (log-rank P=0.025, 0.038, 0.0014 and 0.015, respectively). COL1A1 and FN1 were significantly associated with overall survival (log-rank P=0.013 and 0.05, respectively), and MUC5AC was significantly associated with disease-free survival (log-rank P=0.027). Results from the present study suggested that ASPN, COL1A1, FN1, VCAN and MUC5AC may represent novel prognostic biomarkers for GC.