TY - JOUR
KW - Cell biology
KW - Cell signalling
KW - Diseases
KW - Endocrine system and metabolic diseases
AU - Kyu Shik Mun
AU - Kavisha Arora
AU - Yunjie Huang
AU - Fanmuyi Yang
AU - Sunitha Yarlagadda
AU - Yashaswini Ramananda
AU - Maisam Abu-El-Haija
AU - Joseph J. Palermo
AU - Balamurugan N. Appakalai
AU - Jaimie D. Nathan
AU - Anjaparavanda P. Naren
AB - 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.
BT - Nature Communications
DA - 2019-07-16
DO - 10.1038/s41467-019-11178-w
IS - 1
LA - en
N2 - 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.
PY - 2019
EP - 3124
T2 - Nature Communications
TI - Patient-derived pancreas-on-a-chip to model cystic fibrosis-related disorders
UR - https://www.nature.com/articles/s41467-019-11178-w
VL - 10
Y2 - 2024-03-20
SN - 2041-1723
ER -