Emerging Therapies in Hepatology: Liver-Directed Gene Transfer and Hepatocyte Transplantation

Abstract

Gene transfer and epithelial cell transplantation technologies play an important role in the development of new therapeutic concepts for liver diseases. Although liver organ transplantation has revolutionized the treatment of a wide spectrum of acute and chronic liver diseases, gene- and cell-based therapies are emerging at an astonishing pace, because they promise to be less invasive, less costly and at least as effective as currently established therapy protocols. Experimental gene therapy models have been developed for a wide spectrum of liver diseases, including hereditary liver disorders, malignant liver disease and viral hepatitis. Hepatocyte transplantation (HcTx) is being explored as treatment of severe chronic and acute liver failure as well as for hereditary liver diseases. Most of these procedures and techniques are still experimental or have been applied to a small number of patients only. Rigorous clinical evaluation will finally demonstrate the usefulness of each new procedure in the daily clinical care of patients with liver disease. In this review, we have attempted to provide an introduction and survey of the topics of gene therapy and HcTx with specific examples of laboratory and clinical achievements highlighting potential applications in liver diseases.

Characterization of cell types during rat liver development

“…The interest in hepatic stem cells shifts currently from a proposed involvement in liver carcinogenesis toward the field of experimental therapies for liver diseases: (1) for hepatocyte transplantation and hepatic tissue engineering concepts as a new source for liver tissue and (2) as promising target cells for somatic gene therapy of enzyme deficiency-based metabolic liver diseases. [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.…”

Present status and perspectives of cell-based therapies for liver diseases

“…Nevertheless, cell-based therapies are emerging as an alternative to whole-organ transplantation. Hepatocyte transplantation has been used to bridge patients to whole-organ transplantation [7,69], to decrease mortality in acute liver failure [18,58], and for treatment of metabolic liver disease [3,16,19,22,29,30,47,48,66,67,69]. Cell transplantation is less invasive than whole-organ transplantation and can be performed repeatedly.…”

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

“…3 In view of these shortfalls, cell-based hepatocyte transplantation is of particular interest and believed to hold great promise because of the simpler and less invasive procedure. A single donor could serve multiple recipients, and excess cells could be cryopreserved for future use.…”