In brief

The Steatochip uniformly recreates human liver tissues in miniature and enables precise control of the cellular microenvironment, enhancing drug discovery processes.

© Alexquaas / Wikimedia Commons

One hundred mini livers on a chip

5 Apr 2023

A new microfluidic liver-on-a-chip platform offers drug developers a stable, scalable and sensitive testing ground for much-needed treatments in fatty liver disease.

It may be the only organ in the body that can completely regenerate, but global statistics point to a vulnerable side of the human liver. Up to a quarter of the world’s population lives with non-alcoholic fatty liver disease (NAFLD), an umbrella term for conditions caused by excess fat building up in the liver. Despite being one of the most common liver diseases, NAFLD is often underdiagnosed and lacks approved treatments.

“Early NAFLD is often asymptomatic, with a degree of fat buildup too small to show up on imaging scans,” said Hanry Yu, a Senior Principal Investigator at A*STAR’s Institute of Bioengineering and Bioimaging (IBB). “Many patients get tested only when symptoms manifest, and by then the disease might have already advanced, irreversibly scarring the liver.”

Adding to this, drug development for NAFLD has been limited by the types of experimental liver models currently available to researchers. Animals such as mice might not accurately mirror human NAFLD’s mechanisms, while liver cell cultures from human donors aren’t always suited for high-throughput drug discovery campaigns; these cells can vary between donors and have a relatively short stable lifespan in the lab.

Yu teamed up with researchers from the National University of Singapore (NUS) and the Yong Loo Lin School of Medicine to design an alternative model: the Steatochip, a microfluidic liver-on-a-chip platform for screening hundreds of potential treatments simultaneously.

The team’s main consideration was to miniaturise and capture the human liver’s intricate tissue architecture and labyrinth of blood vessels. Within a single SteatoChip are 100 tiny wells, each nurturing a clump of artificially grown human liver cells called organoids. Like mini livers, these organoids closely simulate their larger real-life counterparts in form and function, whether as healthy or NAFLD-affected tissues.

One key advantage of the SteatoChip is that it maintains a highly controlled environment, creating a reliable platform for testing and comparing treatments.

“The platform is stable enough to allow the long-term in situ formation of liver organoids without always depending on cell cultures,” said Yu. “Compared to other liver models, the cells formed using our method are more homogeneous, which enhances the formation, differentiation and function of liver organoids for more robust drug testing.”

Yu and colleagues put the SteatoChip to the test using an organoid-based model of a liver disease called steatosis. Unlike NAFLD, there are approved medications for steatosis, which the researchers used to show that cells on the chip responded as their live counterparts would.

Through their study, the team established that the SteatoChip is a scalable and highly sensitive drug testing platform with the potential to accelerate drug discovery for NAFLD and other liver conditions. The scientists are currently working towards expanding the chip’s capabilities to tackle more difficult-to-hit liver disease targets.

The A*STAR researchers contributing to this research are from the Institute of Bioengineering and Bioimaging (IBB).

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Teng, Y., Zhao, Z., Tasnim, F., Huang, X. and Yu, H. A scalable and sensitive steatosis chip with long-term perfusion of in situ differentiated HepaRG organoids. Biomaterials 275, 120904 (2021).│article

About the Researcher

Hanry Yu is a Professor of Physiology & Mechanobiology and NUS College at the National University of Singapore; Senior PI at the Institute of Bioengineering and Bioimaging, A*STAR; and Co-lead PI for a MIT research entity in Singapore. He was trained in cell biology but integrates imaging, biomaterials, tissue engineering, drug testing, contextual AI, and mechanobiology to solve problems in GI tract diseases and recently in growing cultivated meat as functional ingredients to improve plant-based meat analogs. He is an award-winning serial technopreneur who strives to build integrated teams to equip future graduates with skills relevant in both industrial and future academic settings. He has taught students in leading universities in the US and Asia.

This article was made for A*STAR Research by Wildtype Media Group