Human foetal hepatocytes: isolation, characterization, and transplantation.

Hepatocyte transplantation has become an alternative to orthotopic liver transplantation for the treatment of liver metabolic diseases. However, there is an increasing lack of donor organs and isolated mature hepatocytes are difficult to manipulate and cannot be expanded in vitro. It is therefore necessary to find alternative sources of hepatocytes, and different approaches to evaluate the therapeutic potential of stem cells of different origins are being developed.

The role of HGF on invasive properties and repopulation potential of human fetal hepatic progenitor cells.

Unlabelled: The success of hepatocyte transplantation has been limited by the low efficiency of transplanted cell integration into liver parenchyma. Human fetal hepatic progenitor cells (hepatoblasts) engraft more effectively than adult hepatocytes in mouse livers. However, the signals required for their integration are not yet fully understood.

Ex vivo liver-directed gene therapy for the treatment of metabolic diseases: advances in hepatocyte transplantation and retroviral vectors.

Transplantation of hepatocytes, whether genetically modified or not, has become an alternative to orthotopic liver transplantation for the treatment of patients with metabolic disease. However, more than ten years after the first clinical trial of ex vivo gene therapy to treat patients with Familial Hypercholesterolemia, there are still a number of impediments to these approaches. Numerous animal models are still being developed on the one hand to improve hepatocyte integration within hepatic parenchyma and function, and on the other hand to develop vectors that drive long-term transgene expression in situ.

Efficient hepatocyte engraftment and long-term transgene expression after reversible portal embolization in nonhuman primates.

Unlabelled: The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as hepatocytes, and portal vein occlusion increases hepatocyte engraftment.

Efficient ex vivo gene transfer into non-human primate hepatocytes using HIV-1 derived lentiviral vectors.

Background/aims: Lentivirus-mediated ex vivo gene therapy is becoming a promising approach for the treatment of liver metabolic disorders. However, the feasibility of this approach needs to be studied in large animal models. The purpose of this study was to evaluate the efficacy of ex vivo gene transfer into Macaca hepatocytes with two different HIV-1 derived lentiviral vectors.

Primate hepatic foetal progenitor cells and their therapeutic potential.

Transplantation of genetically modified or unmodified hepatocytes appears to be a less invasive alternative to liver transplantation. However, clinical trials performed for the treatment of metabolic deficiencies resulted in a partial and transitory correction due to an insufficient number of engrafted and functional hepatocytes. In vitro, adult hepatocytes do not proliferate and the lack of organ donors limits their availability.

Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts.

Transplantation of hepatocytes is a promising alternative to liver transplantation for the treatment of severe liver diseases. However, this approach is hampered by the shortage of donor organs and intrinsic limitations of adult hepatocytes. To investigate whether most of the hurdles faced with adult hepatocytes could be surmounted by the use of human fetal hepatoblasts, we have developed a method to isolate, transduce, and cryopreserve hepatoblasts from human livers at an early stage of development (11-13 weeks of gestation).