Induced pluripotent stem cell-derived mesenchymal stem cells for modeling and treating metabolic associated fatty liver disease and metabolic associated steatohepatitis: Challenges and opportunities

Figure 1 Applications of human induced pluripotent stem cells for nonalcoholic fatty liver/non-alcoholic steatohepatitis disease modeling and therapy. A: Nonalcoholic fatty liver (NAFLD) arises from abnormal lipid accumulation in hepatocytes unrelated to excessive alcohol consumption and is associated with dyslipidemia, insulin resistance, obesity, metabolic syndrome, and type 2 diabetes. The progression of NAFLD to nonalcoholic steatohepatitis (NASH) can be triggered by lipid peroxidation, mitochondrial dysfunction, oxidative stress, hepatocyte apoptosis, the production of proinflammatory cytokines, and alterations in the microbiome. NASH may further deteriorate into cirrhosis due to the development of liver scarring and advanced hepatocellular damage; B: Induced pluripotent stem cells (iPSCs) can be reprogrammed from somatic cells of healthy individuals or patients with NAFLD/NASH; C: Functional hepatocytes, mesenchymal stem cells, and other cell types can be derived from iPSCs for use in regenerative medicine and other therapeutic approaches. Additionally, iPSCs and their derived cells can be characterized and preserved in biobanks worldwide for allogenic cell-based therapies in human leukocyte antigen-matched patients; D: Cells differentiated from iPSCs can be used to create two-dimensional (2D) monocultures, 2D co-cultures, and complex 3D cellular systems, such as liver organoids, to model normal or diseased hepatic tissue. These human in vitro liver models are valuable for studying NAFLD/NASH disease progression as well as for testing drugs to assess their efficacy, safety, and toxicity. If the iPSCs are derived from a patient, these models can help identify drugs with better efficacy for treating that specific patient, enabling personalized medicine. iMSC: Induced pluripotent stem cell-derived mesenchymal stem cell; iHLC: Induced pluripotent stem cell-derived hepatocyte-like cell.