Hepatocyte transplantation: new horizons and challenges

Abstract

Hepatocyte transplantation represents an alternative strategy for treating liver disease. Liver repopulation following acute liver failure could, potentially, eliminate the requirement for orthotopic liver transplantation. Similarly, the ability to repopulate the liver with disease-resistant hepatocytes offers new opportunities for correcting genetic disorders and treating patients with chronic liver disease. Recent advances concerning the fate of transplanted cells in the recipient liver, the efficacy of cell therapy in outstanding animal models of human disease. and the isolation of progenitor liver cells capable of differentiating into mature hepatocytes have renewed optimism in regard to treating people with hepatocyte transplantation. Recruitment of an increasing number of investigators to the field and the success of recent pilot studies indicate that hepatocyte transplantation will become routine clinical practice in the near future.

Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

“…31 Our finding of donor cell engraftment frequencies at 4 weeks post-transplantation was in line with those previously reported. Although differentiation of some of the transplanted donor cells into hepatocytes was detected, consistent with those reported by Sato et al 26 and Aurich et al, 27 the combined findings of predominant repopulation by murine cells, the superior rescuing potential of MSCs over MDHs, as well as the ability to rescue FHF in such a short period suggest that differentiation of donor cells into hepatocytes was not the primary attribute.…”

“…31 By 3 months posttransplantation, human B2M-positive cells were below the sensitivity of detection, and thus we adapted a real-time genomic DNA polymerase chain reaction-based approach previously reported in the literature. 32 Although human cells were detectable by this approach, frequencies were estimated to be 0.001%-0.01% in the liver at both 3 and 6 months posttransplantation, conceivably due to the dilution of donor-derived cells as a result of normal tissue turnover.…”

Differentiation of Embryonic Stem Cells Into Hepatocytes: Biological Functions and Therapeutic Application

“…27,28 Furthermore, the potential ability to replace the liver with genetically modified disease-resistant hepatocytes may offer new insights into correcting genetic disorders and treating patients with chronic liver diseases. 29,30 Although the use of human ES cells for therapeutic purposes must 31,32 to date, convincing results have remained elusive.…”

Characterization of cell types during rat liver development

“…[40][41][42][43][44] A first animal study showed a possible application of isolated fetal hepatocytes for the correction of a metabolic disorder; the intrasplenic transplantation of normal fetal hepatocytes in analbuminemic rats led to a repopulation of the diseased liver with healthy donor hepatocytes and a normalization of albumin levels. 45 The role of fetal liver stem cells for new therapeutic applications has yet to be defined; in addition to the theoretical risks from the use of undifferentiated cells, the legal and ethical issues have to be addressed in the scientific community.…”