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The potential of induced pluripotent stem cells (iPSCs) for modeling and treating metabolic associated fatty liver disease (MAFLD) and metabolic associated steatohepatitis (MASH) is emerging. MAFLD is a growing global health concern, currently with limited treatment options. While primary mesenchymal stem cells hold promise, iPSCs offer a versatile alternative due to their ability to differentiate into various cell types, including iPSC-derived mesenchymal stem cells. However, challenges remain, including optimizing differentiation protocols, ensuring cell safety, and addressing potential tumorigenicity risks. In addition, iPSCs offer the possibility to generate complex cellular models, including three-dimensional organoid models, which are closer representations of the human disease than animal models. Those models would also be valuable for drug discovery and personalized medicine approaches. Overall, iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies. Further research is needed to overcome current limitations and translate this potential into effective clinical applications.

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Core Tip: Induced pluripotent stem cells (iPSCs) show promise for modeling and treating nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. iPSCs can generate various cell types, including cells for therapy or disease modeling. Challenges remain, but iPSCs offer potential for drug discovery and personalized medicine approaches for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

• Citation: Silva B, Bragança J. Induced pluripotent stem cell-derived mesenchymal stem cells for modeling and treating metabolic associated fatty liver disease and metabolic associated steatohepatitis: Challenges and opportunities. World J Stem Cells 2025; 17(2): 99331
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