Stem and progenitor cells for liver repopulation: can we standardise the process from bench to bedside?

Abstract

There has been recent progress in the isolation and characterisation of stem/progenitor cells that may differentiate towards the hepatic lineage. This has raised expectations that therapy of genetic or acquired liver disease might be possible by transplanting stem/progenitor cells or their liver-committed progeny. However, it is currently impossible to determine from the many documented studies which of the stem/progenitor cell populations are the best for therapy of a given disease. This is largely because of the great variability in methods used to characterise cells and their differentiation ability, variability in transplantation models and inconsistent methods to determine the effect of cell grafting in vivo. This manuscript represents a first proposal, created by a group of investigators ranging from basic biologists to clinical hepatologists. It aims to define standardised methods to assess stem/progenitor cells or their hepatic lineage-committed progeny that could be used for cell therapy in liver disease. Furthermore standardisation is suggested both for preclinical animal models to evaluate the ability of such cells to repopulate the liver functionally, and for the ongoing clinical trials using mature hepatocytes. Only when these measures have been put in place will the promise of stem/progenitor-derived hepatocyte-based therapies become reality.

In vitroandin vivomodels of acute alcohol exposure

“…Alcohol also affects the expression of adhesion molecules [135] , which may be a concern when using adherent cell types due to possible cell detachment. Additional concerns arise from the possibility of modified ex vivo function of some primary cells, including hepatocytes, stellate cells and their precursors, due to limited ex vivo environment compared to in vivo conditions [136][137][138] . From a technical point, the acute alcohol exposure of cells in vitro may be hampered by alcohol evaporation.…”

Cirrhosis Model That Tracks Umbilical Cord Mesenchymal Cell Transplantation Using Liver Serum Parameters: A Pilot Study

“…Treatment of acute liver failure caused by partial hepatectomy [35] or a single CCl4 injection [36] has suggested that bone marrow MSC undergo myofibroblast differentiation contributing therefore to progression of fibrosis. Taken together, an overview of the results obtained by several different groups indicates that correct evaluation of liver parameters in preclinical liver disease models is needed and that results obtained may simply reflect in inherent variability of the experimental animals, as already previously noted [37] . In the experiment where data are collected before and after the treatment, the individual variability of serum parameters is evident, though macroscopically the disease is present in all animals.…”

Pluripotent plasticity of stem cells and liver repopulation

“…However, it is currently impossible to determine from the many documented studies which of the stem/progenitor cell populations are the best for therapy of a given disease. 39 The liver, in the healthy adult, such as many other organs maintains a perfect cells gain and loss balance. There are three levels of cells that can respond to loss of hepatocytes:…”