Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development

利用基因编辑技术改造多能干细胞来源的肝细胞,用于肝病建模和治疗开发

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Abstract

The growing demand for physiologically relevant human liver models has driven significant progress in generating hepatic cells and organoids derived from pluripotent stem cells. These regenerative cell sources serve as powerful platforms for elucidating the mechanisms underlying liver diseases and for evaluating drug responses under human-relevant conditions. Moreover, they hold tremendous promise as cell-based therapeutics for various hepatic disorders. The utility of these regenerative cell technologies is further expanded when combined with gene-editing techniques, which enable precise modeling of pathogenic variants and targeted correction of disease-associated mutations. Gene editing can also be leveraged to enhance the functionality and therapeutic potential of regenerative hepatocyte products. In this review, we summarize recent advances at the interface of gene editing and hepatic cell regeneration, emphasizing their applications in genetic disease modeling, therapeutic gene correction, drug testing, and cell-based therapies for liver disorders. We also provide an overview of major gene-editing tools and practical guidance for implementing them in pluripotent stem cells-based regenerative workflows, concluding with future perspectives on the integration of gene editing and regenerative hepatocyte technologies.

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