Concise Review: Updated Advances and Current Challenges in Cell Therapy for Inborn Liver Metabolic Defects

Abstract

Abstract The development of liver cell transplantation (LCT), considered a major biotechnological breakthrough, was intended to provide more accessible treatments for liver disease patients. By preserving the native recipient liver and decreasing hospitalization time, this innovative approach has progressively gained interest among clinicians. LCT initially targets inborn errors of liver metabolism, enabling the compensation of deficient metabolic functions for up to 18 months post-transplantation, supporting its use at least as a bridge to transplantation. The rigorous clinical development and widespread use of LCT depends strongly on controlled and consistent clinical trial data, which may help improve several critical factors, including the standardization of raw biological material and immunosuppression regimens. Substantial effort has also been made in defining and optimizing the most efficient cell population to be transplanted in the liver setting. Although isolated hepatocytes remain the best cell type, showing positive clinical results, their widespread use is hampered by their poor resistance to both cryopreservation and in vitro culture, as well as ever-more-significant donor shortages. Hence, there is considerable interest in developing more standardized and widely accessible cell medicinal products to improve engraftment permanency and post-cell transplantation metabolic effects. Significance In this therapeutic approach to liver disease, new solutions are being designed and evaluated to bypass the documented limitations and move forward toward wide clinical use. Future developments also require a deep knowledge of regulatory framework to launch specific clinical trials that will allow clear assessment of cell therapy and help patients with significant unmet medical needs.