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Nat Commun. 2019 Jul 16;10(1):3124. doi: 10.1038/s41467-019-11178-w.

Patient-derived pancreas-on-a-chip to model cystic fibrosis-related disorders.

Author information

1
Department of Pediatrics, Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
2
Department of Medical Biotechnology, University of Illinois, Rockford, IL, 61107, USA.
3
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
4
Department of Pediatrics, University of Cincinnati, Cincinnati, OH, 45229, USA.
5
Department of Surgery, Center for Cellular Transplantation, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, 40222, USA.
6
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. jaimie.nathan@cchmc.org.
7
Department of Pediatrics, Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. anaren@cchmc.org.

Abstract

Cystic fibrosis (CF) is a genetic disorder caused by defective CF Transmembrane Conductance Regulator (CFTR) function. Insulin producing pancreatic islets are located in close proximity to the pancreatic duct and there is a possibility of impaired cell-cell signaling between pancreatic ductal epithelial cells (PDECs) and islet cells as causative in CF. To study this possibility, we present an in vitro co-culturing system, pancreas-on-a-chip. Furthermore, we present an efficient method to micro dissect patient-derived human pancreatic ducts from pancreatic remnant cell pellets, followed by the isolation of PDECs. Here we show that defective CFTR function in PDECs directly reduced insulin secretion in islet cells significantly. This uniquely developed pancreatic function monitoring tool will help to study CF-related disorders in vitro, as a system to monitor cell-cell functional interaction of PDECs and pancreatic islets, characterize appropriate therapeutic measures and further our understanding of pancreatic function.

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