Researchers at Cincinnati Children’s Hospital Medical Center have developed a human pancreas-on-a-chip to increase our fundamental understanding of the pancreatic function and to identify possible causes of cystic fibrosis-related diabetes (CFRD), a deadly disease common in people with cystic fibrosis (CF).
HUMAN HEALTH ISSUE
Cystic fibrosis-related diabetes (CFRD), which generally presents as disordered glucose metabolism, is a serious disease that affects around half of the people with cystic fibrosis CF in adulthood and it is linked to poor health and premature death.
ANIMAL FREE SCIENCE INNOVATION POTENTIAL
The Pancreas-on-a-chip technology uses patient-derived cells to simulate the human pancreas and allows researchers to facilitate interaction between cells, contributing to a better understanding of the relationship between CF and diabetes and the development of CFRD. This technology can also help researchers discover therapies to manage glucose imbalance in individuals with CF on a highly personalized basis. This highly sensitive, microfluidic device contains a single channel with narrow branches to mimic the pancreatic duct and can detect the defective protein function in pancreatic cells that leads directly to decreased insulin secretion, allowing researchers to better study CFRD disease pathology and physiology. It may also support earlier diagnosis, which can in turn provide opportunity to slow the disease’s progression. Lastly, it could serve as a platform to test therapeutics for CFRD and associated pancreatic disorders.
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.
Source: Russo DP, Strickland J, Karmaus AL, et al. Nonanimal models for acute toxicity evaluations: Applying data-driven profiling and read-across. Environmental Health Perspectives. 2019;127. https://doi.org/10.1038/s41467-019-11178-w