Hepatocyte transplantation in acute liver failure

Abstract

The majority of patients with acute liver failure (ALF) die waiting for orthotopic liver transplantation (OLT). No other treatment modality is shown to improve survival. This study was conducted to assess the safety and feasibility of hepatocyte transplantation (HT) and subsequent engraftment and function of donor cells. Functional and structural integrity of cryopreserved and thawed human hepatocytes were assessed by their morphological characteristics, induction of P-4501A1 transcription, and survival in vivo by xenotransplantation into rats. Five patients with severe ALF underwent intrasplenic (4 patients) and/or intrahepatic (2 patients) HT through angiography under cyclosporine immunosuppression. All patients had grade III to IV encephalopathy and factor V levels less than 0.5 U/mL, were ventilator and dialysis dependent, and were not OLT candidates. Three of the 5 patients who survived 48 hours after HT had substantial improvement in encephalopathy scores, arterial ammonia levels, and prothrombin times. Clinical improvement was paralleled by an increase in aminopyrine and caffeine clearances. All 3 patients lived substantially longer than expected based on clinical experience after HT (12, 28, and 52 days) but eventually died. Postmortem examination showed the presence of transplanted hepatocytes in liver and spleen by light microscopy and fluorescent in situ hybridization (FISH). Cryopreserved and thawed human hepatocytes can be transplanted into recipients with ALF with some acceptable but definite complications. Engraftment of donor hepatocytes was proven by histological examination and FISH by both transjugular biopsy and at autopsy. Improvement in brain edema, encephalopathy grade, and clearance of antipyrine and caffeine suggested function, albeit with a 24- to 72-hour delay posttransplantation.

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

“…The common feature in these diseases is loss or defective hepatocyte function and the only curative therapy is orthotopic liver transplant. However, since there is a severe shortage of suitable donor organs, transplantation of human fetal and adult hepatocytes is being evaluated [3][4][5][6]. However, hepatocyte transplantation is limited by the severe shortage of suitable liver resections for cell isolation, the large number of hepatocytes required for transplantation and difficulties associated with hepatocyte culture and cryopreservation [7].…”

Quantitative Gene Expression Analysis Reveals Transition of Fetal Liver Progenitor Cells to Mature Hepatocytes after Transplantation in uPA/RAG-2 Mice

“…[2][3][4] Stem cells representing a renewable resource for cell transplantation are actively studied for their ability to generate parenchymal cells and tissues and may thus open up new avenues in the treatment of liver disease. When normal reparative pathways of regeneration are impaired, the liver activates a facultative stem cell compartment to restore the liver mass and function.…”

Isolation of human hepatocytes from livers rejected for liver transplantation on a national basis: Results of a 2-year experience

“…Several articles in the literature have reported successful application of allogenic hepatocyte transplantation for acute liver failure and inherited metabolic liver disease. [13][14][15] Moreover, bioartificial liver devices, loaded with animal or human cells, have been used with encouraging results for temporaneous hepatic support of patients affected by fulminant hepatic failure. 16,17 However, the major challenge to the wide clinical application of those methods is represented by the availability of a sufficient amount of live liver cells.…”