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A model of a human liver is placed between a pair of hands, protecting it.
The prevalence of MASH in the United States is estimated to double every 10 years.

3D Printed Tissue Model Could Aid Liver Disease Research

MASH is expected to surpass hepatitis C as the main cause of liver transplantation in the US 

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Metabolic dysfunction-associated steatohepatitis, or MASH, is an inflammatory, liver-scarring disease that has reached epidemic proportions. Around 1.5–6.5 percent of US adults are afflicted by the condition and roughly 24 percent of adults have nonalcoholic fatty liver disease (NAFLD), now called metabolic dysfunction-associated steatotic liver disease (MASLD). 

There are no approved pharmacological therapies for MASH, in part due to a lack of adequate preclinical models for study and testing. In a new paper published in The American Journal of Pathology, researchers at Sanford Burnham Prebys Medical Discovery Institute with colleagues at Viscient Biosciences—a San Diego-based biotech company—and UC San Diego and Salk Institute, described a 3D printed liver tissue model employing liver cells from healthy or MASH-diseased donors. 

“These tissues display all of the characteristics of MASH, including fibrosis, without any additional disease-inducing agents,” said senior and corresponding study author David A. Brenner, MD, president and CEO of Sanford Burnham Prebys and a long-time leader in liver disease research. 

3D printing diseased liver tissues

Co-author Jeffrey Miner, PhD, co-founder and chief scientific officer of Viscient Biosciences, underscored the importance of being able to produce a high-fidelity in vitro human primary cell model of MASH. “This approach utilizes the patient’s own diseased cells, allowing them to generate the disease within the bioprinted tissue. We specifically exclude agents that artificially induce disease. We believe this advance enhances the translation of our results to human clinical trials and drug discovery.”

Researchers were able to create their model by layering a mix of primary liver cells and supporting non-parenchymal liver cells (hepatic stellate, liver sinusoidal endothelial, and Kupffer) to 3D print tissues derived from patient cells.

Notably, the resulting diseased tissues displayed fibrosis, which in the liver results in progressive scarring and dysfunction and leads to cirrhosis and liver cancer. With no way to stop or reverse fibrosis, the only recourse is an organ transplant.

The new models offered a peek at the underlying pathology, illuminating the roles of hepatic stellate and liver sinusoidal endothelial cells in the disease process. “This model represents a fully human system with the potential to detect clinically active targets and therapies,” said Miner. “That’s important given that current discovery and animal models have not translated into any approved drugs.”

- This press release was originally published on the Sanford Burnham Prebys website