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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Shik Mun K,Arora K,Huang Y,Yang F,Yarlagadda S,Ramananda Y,Abu-El-Haija M,Palermo JJ,Appakalai BN,Nathan JD,Naren AP

doi

10.1038/s41467-019-11178-w

subject

Has Abstract

pub_date

2019-07-16 00:00:00

pages

3124

issue

1

issn

2041-1723

pii

10.1038/s41467-019-11178-w

journal_volume

10

pub_type

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