3D Bioprinted Model of Nonalcoholic Steatohepatitis (NASH)

Key Points:

Researchers developed a 3D bioprinted liver tissue model using healthy individuals and nonalcoholic steatohepatitis cells.
The model demonstrates the significant roles of hepatic stellate and liver sinusoidal endothelial cells in the progression of NASH.
This innovative approach holds the potential for identifying new therapeutic targets and treatments.

A stained micrograph of 3D primary human liver cell tissue modeling NASH. Areas of fibrosis are indicated in blue—image courtesy of Viscient Biosciences.

Overview

Metabolic Dysfunction-Associated Steatohepatitis (MASH), previously known as Nonalcoholic Steatohepatitis (NASH), is an increasingly prevalent liver disease. It is a severe form of Nonalcoholic Fatty Liver Disease (NAFLD), which affects a significant percentage of the adult population. These diseases are now grouped under Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD).

Despite its growing prevalence, no approved pharmacological treatments for Nonalcoholic Steatohepatitis (NASH) exist. This is partly due to a lack of effective preclinical models. Currently, the only treatment for advanced fibrosis associated with this condition is organ transplantation.

Nonalcoholic steatohepatitis bio-printed model

To solve this problem, researchers have developed a three-dimensional bio-printed liver tissue model using primary human hepatocytes and non-parenchymal cells (hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) from both healthy and Nonalcoholic Steatohepatitis (NASH) donors. Tissues bio-printed with cells from NASH patients successfully replicated the disease’s characteristics, including fibrosis, without the need for external disease-inducing agents.

In contrast, tissues composed of healthy cells showed markedly less disease evidence. The research also explored the specific roles of different cell types in nonalcoholic steatohepatitis (NASH) by creating chimeric tissues with various combinations of healthy and diseased cells. This novel approach highlights the roles of hepatic stellate and liver sinusoidal endothelial cells in NASH progression.

Implications

Researchers highlight the model’s potential for identifying active targets and therapies for liver disease. The model’s faithfulness to human physiology makes it a promising tool for identifying effective treatments for this challenging condition.

References

Tan, Philip K., Traci Ostertag, Sara B. Rosenthal, Daisy Chilin-Fuentes, Haylee Aidnik, Sara Linker, Keith Murphy, Jeffrey N. Miner, and David A. Brenner. 2023. “Role of Hepatic Stellate and Liver Sinusoidal Endothelial Cells in a Human Primary Cell Three-Dimensional Model of Nonalcoholic Steatohepatitis.” The American Journal of Pathology 0 (0). https://doi.org/10.1016/j.ajpath.2023.12.005.
A New 3D Bioprinted Model Offers a Novel Tool to Study Common Liver Disease, and Perhaps Find an Effective Treatment | Sanford Burnham Prebys.” 2024. January 23, 2024. https://sbpdiscovery.org/news/a-new-3d-bioprinted-model-offers-a-novel-tool-to-study-common-liver-disease-and-perhaps-find.

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