Hepatocyte transplantation as a treatment for glycogen storage disease type 1a

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

“…An infusion of isolated hepatocytes through the portal vein equivalent to 5% of the parenchymal mass to a patient with Crigler-Najjar syndrome achieved a medium-term reduction in serum bilirubin and increased bilirubin conjugate levels in the bile [43]. Hepatocyte transplantation has also been successful in the treatment of human glycogen storage disease type 1a [44], but not in the treatment of severe ornithine transcarbamylase deficiency, where rejection of the transplanted cells was thought to be the reason for only temporary (11 days) relief [45]. Also, a temporary, but impressive, reduction in the requirement for exogenous recombinant factor VII was achieved by transplantation of adult hepatocytes to two children with inherited severe factor VII deficiency, although orthotopic liver transplants were required by both recipients after 6 months [46].…”

Liver gene therapy: advances and hurdles

“…69,71 Most recently, three studies also demonstrated metabolic benefits after hepatocyte transplantation in a patient with glycogen storage disease type 1a, with severe OTC and with peroxymal biogenesis disease. 70,72,73 These studies also showed that: (i) transplantation of normal hepatocytes as few as 1% of the patient liver mass could lead to metabolic benefits; 73 (ii) hepatocyte transplantation was safe in babies, therefore raising perspectives for ex vivo gene therapy in early stages of liver diseases; 70 (iii) repeated hepatocyte infusions (fresh and/or cryopreserved hepatocytes) allowed to obtain metabolic benefits; 70,72 and (iv) hepatocyte transplantations were insufficient to fully correct the metabolic liver diseases, therefore re-emphasizing the limitations of hepatocyte transplantation, in particular the inefficient repopulation of the recipient liver by donor cells. 1,74,75 Understanding the transplantation mechanisms, engraftment and repopulating ability of transplanted hepatocytes is therefore critical for defining suitable strategies to increase the transplanted hepatocyte mass.…”

Liver stem cells: prospects for treatment of inherited and acquired liver diseases

“…The latter category includes metabolic deficiencies (e.g., Crigler-Najjar syndrome, familial hypercholesterolaemia and amyloidosis, oxalosis) and coagulation defects (haemophilia A, Factor IX deficiency). Therapeutic hepatocyte transplantation has been accomplished in a limited number of such patients [55][56][57].…”

“…Acquired liver diseases, particularly acute failure secondary to toxic or viral injury, have been treated in limited clinical trials with fetal and adult hepatocytes [57][58][59][60][61][62][63]. The efficacy of these treatments in helping patients to survive until a donor organ becomes available, with improvement of clinical measures such as hepatic encephalopathy and cerebral perfusion pressures, is promising but not yet clear.…”