Pancreas-on-a-chip boosts cystic fibrosis research

The latest innovation in organs-on-chips is the pancreas-on-a-chip, which incorporates 3D organoid technology to enhance the chip’s performance. It was developed by scientists at the Cincinnati Children’s Hospital Medical Center to study life-threatening cystic-fibrosis-related diabetes, a common complication for cystic fibrosis (CF) patients.  

The study, published in Nature Communications, finds that this in-vitro model of the human pancreas has enormous potential to elucidate the causes of CF related diabetes, while also noting the failures and limitations of previous animal research.

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In order to recreate a human pancreas, researchers placed organoids derived from donated human pancreas cells into dual-chambered organ chips. Next they genetically engineered some of these cells to disrupt the suspected faulty gene. This resulted in impaired cell-to-cell communications, fluid exchange and hormone release problems and ultimately insulin deficiency, confirming that the suspected gene has a direct role in causing diabetes in cystic fibrosis patients. 

This advancement came only after researchers switched to the human-based pancreas-on-a-chip.  Anjaparavanda Naren, PhD, the study’s principal investigator, said “Mouse models of CF don’t faithfully recreate CF-related diabetes in the lab, and it wasn’t possible to study the disease at the depth we achieved in this study”.

“Our technology closely resembles the human pancreas and potentially may help us find therapeutic measures to manage glucose [sugar] imbalance in people with CF,” he concluded.

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This is in stark contrast to mouse studies which are irrelevant and inhumane.

In one experiment to study cystic fibrosis, mice were sedated and hung by their front teeth from a plastic device created to administer inhaled compounds. Their noses were blocked and their tongues clamped with forceps, while the dose was sprayed down their throats. The mice underwent this procedure three times over six days before being finally killed by asphyxiation with carbon dioxide gas, a process in which fully conscious animals slowly suffocate to death.

penn century inc

Dr. Naren and his research team are hopeful that future experiments utilizing the human-relevant pancreas-on-a-chip will not only effectively manage glucose imbalance but can also serve as a monitoring tool to help understand a range of cystic fibrosis disorders.

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