In a recent work published in BME Frontiers, a collaborative study by researchers from Griffith University, Queensland University of Technology, University of Queensland, and Nanjing Stomatological Hospital has introduced groundbreaking three-dimensional (3D) dynamic cell co-culture models to simulate metabolic dysfunction-associated steatotic liver disease (MASLD) progression stages. This innovation addresses limitations of traditional 2D cell cultures in modeling complex liver pathologies.
MASLD, a prevalent chronic condition affecting approximately 30% of the global population, progresses through stages including simple steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis, ultimately leading to hepatocellular carcinoma (HCC). Traditional in vitro models, such as 2D hepatocyte monocultures, have failed to replicate the complex interactions among multiple cell types and dynamic environments observed in vivo.
The research utilized a novel 3D dynamic coculture system incorporating a mini-bioreactor. Three distinct MASLD models were established: steatosis (hepatocytes only), MASH (hepatocytes and macrophages), and fibrosis (hepatocytes, macrophages, and hepatic stellate cells). Validation against high-fat-diet mouse models confirmed progressive hepatocyte viability decline and lipid accumulation, mirroring in vivo pathology. Gene expression profiles aligned closely with MASLD-affected livers.
Key findings highlight pro-inflammatory macrophages as drivers of hepatocyte lipid metabolism disruption. The 3D system allows cell-specific response analysis and accelerates MASLD phenotype onset within 24 hours, significantly enhancing research efficiency.
This advancement not only enhances mechanistic understanding but also empowers precision medicine. Future studies may leverage these models to explore personalized treatments, optimizing outcomes for patients across MASLD's spectrum. With its potential to transform therapeutic discovery, this work stands at the forefront of hepatology research, offering renewed hope for millions affected by liver disease.
