Induction of MASH in three-dimensional bioprinted human liver tissue

Area of Science:

• Regenerative Medicine
• Hepatology
• Bioprinting Technology

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease leading to cirrhosis and liver cancer.
• Current MASH models are insufficient for understanding disease mechanisms and developing new therapies.
• There is a critical need for advanced in vitro models that accurately mimic human MASH.

Purpose of the Study:

• To develop a novel, complex multicellular 3D bioprinted human liver tissue model for MASH research.
• To create a platform for studying MASH pathophysiology and facilitating drug discovery.
• To generate a physiologically relevant MASH model using advanced bioprinting techniques.

Main Methods:

• Utilized complex multicellular 3D bioprinting to combine hepatocytes with nonparenchymal liver cells (endothelial, Kupffer, stellate cells) in precise ratios.
• Developed biocompatible hydrogel bioinks for tissue fabrication.
• Incubated bioprinted tissues in a MASH-inducing media cocktail (fatty acids, LPS, fructose) and compared to control tissues.
• Performed histological processing and transcriptome analysis to assess MASH development and compare to patient biopsies.

Main Results:

• Bioprinted human liver tissues successfully developed a MASH phenotype, including hepatocyte steatosis, inflammation, and fibrosis, upon induction.
• The developed MASH tissues exhibited transcriptome profiles significantly similar to human MASH patient biopsies.
• The bioprinted tissues were of sufficient size and quality for detailed histological and immunohistochemical analysis.

Conclusions:

• A 3D bioprinted human liver tissue model accurately recapitulates key features of MASH.
• This innovative model provides a powerful tool for advancing MASH pathophysiology research.
• The bioprinted MASH liver tissue is suitable for preclinical drug screening and development.