Cell-Based Therapies for Liver Disease: From Transplantation to Regenerative and Immuno-Engineered Solutions
Christian Williams and Fang Xiao*
Liver disease remains a major global health challenge, with chronic and acute liver failure continuing to drive high morbidity and mortality. The current standard of care for end stage liver disease is allogeneic liver transplantation combined with long term immunosuppressive therapy. Although lifesaving, transplantation is constrained by immune mediated graft rejection, surgical complications including reperfusion injury, off target toxicities of immunosuppressants such as nephrotoxicity, and severe donor organ shortages. These limitations have intensified efforts to develop regenerative strategies that harness the liver’s intrinsic repair mechanisms. This review provides an integrated overview of emerging cell-based therapies for liver regeneration, including primary hepatocytes, hepatic progenitor cells, mesenchymal stem cells, and induced pluripotent stem cell derived hepatocytes. We highlight the growing importance of immune cell–based approaches, such as Kupffer cells, dendritic cells, and tolerogenic dendritic cells, which regulate inflammation, promote immune tolerance, and remodel the hepatic microenvironment to support repair. We critically evaluate the strengths, limitations, and translational barriers associated with each cell category, including sourcing, scalability, immunogenicity, and therapeutic durability. Advances in organoid-based liver models and liver like constructs are also discussed, with emphasis on their potential for personalised therapy, immune education, and biobanked regenerative products. This review synthesises current evidence, highlights key challenges, and outlines future directions for integrating cell therapies, immune‑modulating strategies, and organoid technologies into clinical practice. Altogether, these regenerative and immuno‑engineered innovations might signal a shift away from traditional transplantation toward more precise and functional restoration of the diseased liver.
