Modeling Human Liver Steatosis in Induced Pluripotent Stem Cell-Derived Liver Spheres

Alterations in cellular metabolism are a major contributor to the worldwide obesity crisis. Numerous defects underpin this disease, and a major contributor is the development of metabolic dysfunction associated with steatotic liver disease (MASLD). This can lead to the progressive form of liver disease termed Metabolic Dysfunction Associated Steatohepatitis (MASH) and this can lead to end-stage liver disease (Wong VWS, Adams LA, de Ledinghen V et al, Nat Rev Gastroenterol Hepatol 8:461-478, 2018). While liver transplantation is highly successful at treating end-stage liver disease, it is severely limited by organ donation and limited by the requirement for life-long immunosuppression. Therefore, to better understand the disease, and identify new biomarkers, and therapeutics for MASLD/MASH, new human cell-based models are required (Wong VWS, Adams LA, de Ledinghen V et al, Nat Rev Gastroenterol Hepatol 8:461-478, 2018). Therefore, we have developed a scalable liver tissue engineering platform from induced pluripotent stem cells (iPSCs) to study human liver metabolic disease in vitro.