Human hepatocyte transplantation for liver disease: current status and future perspectives

Abstract

Liver transplantation is the accepted treatment for patients with acute liver failure and liver-based metabolic disorders. However, donor organ shortage and lifelong need for immunosuppression are the main limitations to liver transplantation. In addition, loss of the native liver as a target organ for future gene therapy for metabolic disorders limits the futuristic treatment options, resulting in the need for alternative therapeutic strategies. A potential alternative to liver transplantation is allogeneic hepatocyte transplantation. Over the last two decades, hepatocyte transplantation has made the transition from bench to bedside. Standardized techniques have been established for isolation, culture, and cryopreservation of human hepatocytes. Clinical hepatocyte transplantation safety and short-term efficacy have been proven; however, some major hurdles-mainly concerning shortage of donor organs, low cell engraftment, and lack of a long-lasting effect-need to be overcome to widen its clinical applications. Current research is aimed at addressing these problems, with the ultimate goal of increasing hepatocyte transplantation efficacy in clinical applications.

Disease burden of Crigler–Najjar syndrome: Systematic review and future perspectives

“…22,35 Leakage at the bile duct anastomosis was reported as a specific complication following a living donor transplant for CNS. 35 Hepatocyte transplantation, in which between 5% and 15% of the host liver is replaced with transplanted hepatocytes, 48,49 and gene therapy, including injections of naked plasmid DNA and the use of adeno-associated virus (AAV) vectors, 50 are currently being investigated as potential therapies for CNS. These approaches show some promise in preclinical models, [51][52][53][54] but to date, liver transplantation remains the only curative therapy for CNS-I.…”

Acute Liver Failure

“…However, present challenges include a reduced cell source, decreased cell viability following cryopreservation, and poor engraftment of cells into the recipient liver with consequently a limited lifespan. 127,133,134 Therefore, alternative stem cell sources including pluripotent stem cells, fibroblasts, hepatic progenitor cells, amniotic epithelial cells, and mesenchymal stem/stromal cells can be introduced to generate induced hepatocyte-like cells, with each technique exhibiting advantages and disadvantages. Mesenchymal stem/stromal cells transplantation had beneficial effects, especially in ACLF patients.…”

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“…Transplant remains the only viable option for many of these patients; however, donor tissue availability remains scarce. One potential treatment option for some patients is utilizing primary hepatocytes for allogenic transplantation, but obtaining enough high‐quality donor cells has proved challenging . Utilizing human induced pluripotent stem cells (hiPSC) to generate functional hepatocytes in clinically significant numbers is a promising approach.…”