Improvement of liver cirrhosis using hepatocyte-derived liver progenitor-like cells (HepLPCs): a prospective, open label, single arm, safety trial
The escalating demand for liver transplantation, coupled with the scarcity of donor organs and inherent transplantation risks, underscores the urgent need for innovative cirrhosis treatments. To address this, we have developed a protocol for transforming human primary hepatocytes into expandable Hepatocyte-Derived Liver Progenitor-Like Cells (HepLPCs). In animal models, these cells exhibited anti-fibrotic properties and facilitated liver regeneration. This study comprises a pre-clinical phase and an inaugural clinical trial involving nine cirrhosis patients to assess the feasibility and safety of HepLPC treatment. The HepLPCs infusion was well-tolerated, devoid of transfusion reactions or dose-limiting toxicities. Primary outcome measures, encompassing safety and feasibility, were successfully met. Notably, the results revealed enhanced liver function following HepLPCs infusion, indicating significant improvements in cirrhosis indicators over a 6-month observation period. These promising findings advocate for the therapeutic potential of HepLPCs as an innovative strategy for liver cirrhosis, warranting further exploration through clinical trials, particularly in decompensated cirrhosis and acute-on-chronic liver failure patients. Overall design: global expression analysis of RNA sequencing data of expression levels of human hepatocytes and expandable hepatocytes derived liver progenitor-like cells state (designated as HepLPCs)