Research News

Researchers Established Efficient Expansion and CRISPR-Cas9-Mediated Gene Correction of Patient-Derived Hepatocytes for Treatment of Inherited Liver Diseases

Source: Time: 2024-05-21

In a study published in Cell Stem Cell, teams led by Dr. HUI Lijian from the Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, collaborated with Dr. XIA Qiang from Renji Hospital, Dr. LI Dali from East China Normal University, and Dr. ZHONG Guisheng from iHuman Institute, ShanghaiTech University, have established an efficient in vitro culture system for hepatocytes derived from patients with inherited metabolic liver diseases. It achieved long-term and large-scale expansion of hepatocytes from various genetic liver disorders.

Building upon this foundation, the researchers optimized and developed CRISPR-Cas9-mediated gene editing techniques, enabling efficient targeted correction of patient-defective genes within proliferating human hepatocytes (ProliHHs) derived from patients with inherited metabolic diseases.

Furthermore, transplantation of gene-edited ProliHHs efficiently integrated and repopulated in mouse livers, successfully treating a tyrosinemia mouse model, thereby demonstrating the effectiveness of ex vivo gene-corrected ProliHHs therapy.

In summary, this study established a set of efficient in vitro culture and gene editing techniques for hepatocytes derived from patients with genetic liver diseases, providing conceptual validation for autologous hepatocyte therapy in human genetic liver diseases.