tailieunhanh - Báo cáo y học: " Airway branching morphogenesis in three dimensional culture"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:Airway branching morphogenesis in three dimensional culture. | Franzdottir et al. Respiratory Research 2010 11 162 http content 11 1 162 RESPIRATORY RESEARCH RESEARCH Open Access Airway branching morphogenesis in three dimensional culture Sigrídur R Franzdottir 1 Ivar T Axelsson1 Ari J Arason1 Ólafur Baldursson4 Thorarinn Gudjonsson1 3 Magnus K Magnusson1 2 3 Abstract Background Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional 3D co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. Methods We used a human bronchial epithelial cell line VA10 recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype expressing p63 and other basal markers such as cytokeratin-5 and -14. Here we cultured VA10 with human umbilical vein endothelial cells HUVECs to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy immunostainings and confocal imaging. Results We found that in co-culture with endothelial cells the VA10 cells generated bronchioalveolar like structures suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore fibroblast .