干细胞研究与治疗杂志

抽象的

Modeling Liver Diseases Using Induced Pluripotent Stem Cell (Ipsc)-Derived Hepatocytes

Joseph Ignatius Irudayam, Deisy Contreras, Sudhakar Sivasubramaniam and Vaithilingaraja Arumugaswami

The induced pluripotent stem cells (iPSCs) are reprogrammed somatic cells in a stem state. The iPSCs can give rise to cells of all three germ layers and provide an unlimited supply of tissue-specific differentiated cell types for disease modeling and cell therapy. The generation of patient-specific iPSC lines and studying disease phenotype in a dish using differentiated hepatocytes open up new avenue towards personalized medicine. There has been active investigation on generating homogenous functional human hepatocytes from iPSCs. Liver carries out secretory and metabolic functions. Recent studies showed that iPSC derived-human hepatocytes are useful for in vitro investigation of genetic liver disorders, drug screening and metabolism, hepatitis C viral infection and assessing efficacy of cell therapy. Inherited metabolic disorders, including α1-antitrypsin deficiency (A1AD), familial hypercholesterolemia, glycogen storage disease type 1a and Wilson’s disease have been modeled using disease-specific iPSC lines. The iPSC hepatocytes derived from patients with A1AD were used for drug screening. Advancement made in precise genetic engineering technology using designer nucleases provides a new tool for gene correction, and reverse genetic engineering of disease causing genotype in pluripotent stem cells. Moreover, iPSC-hepatocytes from various genetic backgrounds are valuable resource for evaluating drug interactions and drug metabolism. In this review, we summarize the recent developments on the various applications of iPSC-derived human hepatocytes for disease modeling.