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- W2512623047 abstract "Exocrine/ductal pancreatic differentiation from human pluripotent stem cells is a poorly understood process albeit various diseases arise from this compartment. We designed a straightforward approach to direct human pluripotent stem cells (PSC) toward pancreatic organoids resembling exocrine and ductal progeny. Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultra-structural and functional hallmarks of human pancreas in the dish. Upon orthotopic transplantation into immunodeficient mice, these organoids form normal pancreatic ducts and acinar tissue resembling fetal human pancreas without any evidence of tumour formation or transformation. Finally, we implemented this unique phenotyping tool as a model for pancreatic facets of cystic fibrosis (CF) but also other inherited pancreatic disorders. We provide for the first time evidence that pancreatic commitment occurs generally unhindered in CF. Importantly, CFTR-activation in mutated pancreatic organoids mirrors the CF-phenotype in a series of functional assays. We also conducted a scalable proof-of concept screen in CF-pancreatic organoids using a set of CFTR correctors and activators. Finally, we did orthotopic transplantation of CF-organoids to generate diseased human pancreata in mice and established a mRNA-mediated gene therapy approach in CF-organoids. Similar assays were applied to another inherited pancreatic disorder. Thus, our platform provides novel opportunities to model pancreatic disease and development but also to screen for disease rescuing agents." @default.
- W2512623047 created "2016-09-16" @default.
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- W2512623047 date "2016-08-16" @default.
- W2512623047 modified "2023-09-26" @default.
- W2512623047 title "Human pluripotent stem cell-derived exocrine/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling" @default.
- W2512623047 doi "https://doi.org/10.1055/s-0036-1587235" @default.
- W2512623047 hasPublicationYear "2016" @default.
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