Human pluripotent stem cell-derived exocrine/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling

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…