This invention is a human liver organoid model derived from induced pluripotent stem cells (iPSCs) that replicates the cellular complexity of the human liver. The system is designed to include multiple liver cell types, without genetic manipulation or animal derived matrices, enabling more accurate modeling of liver diseases such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and its advanced form Metabolic Dysfunction-Associated Steatohepatitis (MASH). Unlike animal models, these organoids closely reflect human biology, making them an ideal platform for disease modeling, drug screening, and therapeutic discovery. Background: Liver disease accounts for approximately two million deaths annually, highlighting a significant burden that remains sub-optimally managed in part due to a chronic shortage of donor organs. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a liver disorder caused by chronic deposition of fat in the liver, while Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a progression of MASLD where inflammation and liver cell damage occur. Currently, 38% of all adults and 7-14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%. This situation necessitates urgent exploration of potential alternatives to bridge this gap. Current models including 2D cell cultures and animal studies, fall short in mimicking the full cellular complexity and human relevance of these diseases. Applications:
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