Advancing hepatocyte-based therapies: A translational perspective.

Hepatocyte-based therapies represent a promising alternative to liver transplantation, yet their clinical translation is constrained by the limited availability of functional cells and inefficient engraftment. Here, we review progress in the field from a translational perspective, focusing on strategies to overcome these core challenges. We analyze emerging cell sources derived from stem cell technologies and assess their therapeutic potential. These translational efforts are organized around two clinical paradigms: hepatocyte replacement for long-term functional correction and temporary hepatocyte support for liver failure. Beyond hepatocytes, we also discuss preclinical and translational advances involving other liver cell types. To conclude, we outline critical gaps that need to be addressed for clinical translation, including scalable good manufacturing practice (GMP)-compliant manufacturing, efficient preconditioning regimens, long-term immune compatibility with non-invasive graft monitoring, and patient stratification for optimal clinical outcomes. We also discuss how hepatocyte-based therapies can complement gene/RNA therapies and xenotransplantation to broaden treatment options for liver diseases.