The quest for liver progenitor cells: A practical point of view

Many chronic liver diseases can lead to hepatic dysfunction with organ failure. At present, orthotopic liver transplantation represents the benchmark therapy of terminal liver disease. However this practice is limited by shortage of donor grafts, the need for lifelong immunosuppression and very demanding state-of-the-art surgery. For this reason, new therapies have been developed to restore liver function, primarily in the form of hepatocyte transplantation and artificial liver support devices. While already offered in very specialized centers, both of these modalities still remain experimental. Recently, liver progenitor cells have shown great promise for cell therapy, and consequently they have attracted a lot of attention as an alternative or supportive tool for liver transplantation. These liver progenitor cells are quiescent in the healthy liver and become activated in certain liver diseases in which the regenerative capacity of mature hepatocytes and/or cholangiocytes is impaired. Although reports describing liver progenitor cells are numerous, they have not led to a consensus on the identity of the liver progenitor cell. In this review, we will discuss some of the characteristics of these cells and the different ways that have been used to obtain these from rodents. We will also highlight the challenges that researchers are facing in their quest to identify and use liver progenitor cells.

Keywords: Liver progenitor cells, Oval cells, Liver regeneration, Liver injury, Stem cells

Abbreviations: DNA, deoxyribonucleic acid, LPC, liver progenitor cell, CCl₄, carbotetrachloride, AAF, 2-acetylaminofluorene, APAP, N-acetyl-p-aminophenol, SCF, stem cell factor, SDF1, stromalcell-derived factor-1, CXCR4, CXC chemokine receptor4, TWEAK, tumor necrosis factor-like weak inducer of apoptosis, KT, cytokeratin, ALB, albumin, AAT, alpha anti-trypsine, CD, cluster of differentiation, AFP, alpha fetoprotein, N-CAM, neural-cell adhesion molecule, Thy-1, thymus antigen 1, Sca-1, stem cell antigen 1, BM, basal membrane, ECM, extracellular matrix, IL, interleukin, TNF, tumor necrosis factor, CDE, choline-deficient, ethionine-supplemented diet, AA, allyl alcohol, PH, partial hepatectomy, EpCAM, epithelial cell adhesion molecule, ABCG2, ATP-binding-cassette transporter-G2, PF, parenchymal fraction, NPF, non-parenchymal fraction, MACS, magnetic activated cell sorting, FACS, fluorescence-activated cell sorting, SP, side population, LCM, laser capture micro-dissection, FAH, fumarylacetoacetate hydrolase, GFP, green fluorescent protein, DDC, 3-diethoxycarbonyl-1,4-dihydrocollidine, DIPIN, 1,4-bis[N,N′-di(ethylene)phosphamide]piperazine, DEN, diethylnitrosamine, CCRP, core circadian regulatory protein, HNF, hepatocyte nuclear factor, Cx, Connexin, MPK, muscle pyruvate kinase, GST, glutathione S transferase, GGT, gamma glutamyl transpeptidase, Dlk, delta-like protein, Chrom-A, Chromogranin A