Hepatocyte Transplantation: Quo Vadis?

Area of Science:

• Hepatology
• Regenerative Medicine
• Gene Therapy

Background:

• Orthotopic liver transplantation (OLT) is effective for end-stage liver disease but faces limitations like organ shortage and lifelong immunosuppression.
• Hepatocyte transplantation (HT) presents a potentially less invasive alternative, enabling personalized medicine via autologous cell modification.
• Key challenges for HT include cell source availability, efficient ex vivo gene therapy, and successful cell engraftment and repopulation.

Purpose of the Study:

• To review advancements in cell sources, gene therapy, and engraftment strategies for hepatocyte transplantation.
• To discuss novel approaches including lineage reprogramming and hepatic irradiation-based preparative regimens.
• To present initial results from patients with genetic liver disorders undergoing hepatic irradiation prior to hepatocyte transplantation.

Main Methods:

• Review of literature on lineage reprogramming for generating transplantable liver cells.
• Evaluation of clinically applicable ex vivo gene therapy techniques for hepatocytes.
• Analysis of hepatic irradiation as a preparative regimen to enhance cell engraftment and repopulation.
• Case review of the first three patients with genetic liver disorders receiving hepatic irradiation and hepatocyte transplantation.

Main Results:

• Emerging strategies for generating transplantable liver cells through lineage reprogramming are discussed.
• Clinically relevant gene therapy methods for hepatocyte modification are being developed.
• Hepatic irradiation shows promise in enhancing the engraftment and repopulation of transplanted hepatocytes.
• Preliminary data from three patients suggest the feasibility of hepatic irradiation followed by hepatocyte transplantation for genetic liver disorders.

Conclusions:

• Overcoming challenges in cell sourcing, gene therapy, and engraftment is crucial for advancing hepatocyte transplantation.
• Lineage reprogramming and hepatic irradiation represent promising avenues for improving HT efficacy.
• Early clinical experience indicates that hepatic irradiation may facilitate successful hepatocyte transplantation in patients with genetic liver diseases.