New tissue models may aid drug research for liver disease

MIT engineers report a liver microphysiological model that recreates blood vessels and immune cell circulation and reproduces early inflammation and metabolic dysfunction seen in MASLD, according to papers in Nature Communications and Communications Biology.

More than 100 million people in the United States are reported to have metabolic dysfunction-associated steatotic liver disease (MASLD), a condition marked by fat buildup in the liver that can lead to inflammation and fibrosis. MIT engineers have designed a new microphysiological liver model that includes blood vessels and allows immune cells to circulate through the tissue. The team published results in Nature Communications and has related findings in Communications Biology that examined drug responses in an earlier model. The work aims to provide a human-based platform for studying early disease processes and drug interactions that are hard to reproduce in animals. Key findings: - The new chip supports growth of a microvascular network into liver tissue and permits circulation of immune cells through that tissue. - Researchers induced insulin resistance in the model by exposing tissues to high insulin, glucose, and fatty acids, producing fat accumulation and metabolic changes seen in MASLD. - The model showed increased inflammatory markers and monocyte recruitment in the insulin-resistant state, reflecting immune features of early liver disease. - In a related study, treatment with the drug resmetirom produced increased immune signaling in the earlier LiverChip model, which the authors note may help explain variable patient responses. - The senior author is Linda Griffith; lead authors include Erin Tevonian, Ellen Kan, and Dominick Hellen, and the work was funded by agencies including the NIH and NSF. Summary: The studies describe a more anatomically and immunologically realistic human liver model that reproduces aspects of early MASLD and can be used to study drug responses. The papers report differences in immune interactions between healthy and insulin-resistant tissue and note a paradoxical inflammatory response to resmetirom in the earlier model. Undetermined at this time.