Mini liver organoid models emulating metabolic dysfunction-associated steatotic disease development: gradually emerging beneath the iceberg

Tissue spatial interaction in the liver, including the interplay among immune cells, blood vessels, sinusoidal endothelial cells, bile ducts, stellate cells, hepatic progenitor cells, and hepatocytes, is crucial not only for normal organogenesis but also for disease development. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent liver disease, with heterogeneous mechanisms involving crosstalk between hepatocytes and stromal cells under metabolic stress, inflammation, and fibrosis. Developing 3D coculture liver organoid platforms provides novel insights into the complex links of cell communication during disease progression. Thus, we recapitulate liver organoids as models for indicating reconstructed inter-tissue interactions of MASLD, highlighting the potential of transplanting liver organoids as a therapeutic application.