Restoring balance to liver stem cell research

Abstract

This month’s report from Saji et al., entitled ‘Basic fibroblast growth factor promotes the trans-differentiation of mouse bone marrow cells into hepatic lineage cells via multiple liver-enriched transcription factors’ [1], is one of a handful of recent papers helping to restore balance to the contentious field of adult stem cell research in general and, more specifically, to investigations of liver stem/progenitor cells and the roles played by different mechanisms of cell plasticity in hepatic responses to injury. Since the field first exploded with publications indicative of unexpected adult stem cell plasticity in 1999, several challenges to the findings have arisen, forcing ever more careful demonstrations and analyses of the phenomena [2]. These, in turn, have lead to more nuanced understandings of cell differentiative potential, both in vivo and ex vivo. The first challenge to the field, of course, was reproducibility. Though some negative results papers have been published, the negative findings have often proven to be based on differences in study design rather than a true lack of reproducibility of the underlying mechanisms (for an example see Wagers et al. and Technical Comments on that paper [3,4]). Virtually all of the in vivo studies have involved transplantation experiments, either of bone marrow or of the target organ of interest. Many variables in study design may contribute to differences in outcomes, but these are rarely discussed in the experimental reports or in reviews and commentaries. Some of these variables are uncontrolled physiological aspects of the study designs, including the respective ages of the donors and recipients, differences between strains and between species, and differences in the selection criteria and pre-conditioning of the donor cells (selection methods themselves being initial steps of preconditioning), and the varied models of injury employed to heighten the possibility of plasticity. The different techniques used to detect and quantify engraftment and plasticity