Developing defined substrates for stem cell culture and differentiation

Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell –matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’

Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells

Acknowledgments BLV and DCH were funded by an award from the Chief Scientist Office (TCS 16/37). This work has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 681002 (EU-ToxRisk) and from TransQST (no. 116030).Peer reviewedPublisher PD

Quantification of ethyl glucuronide, ethyl sulfate, nicotine, and its metabolites in human fetal liver and placenta

This research was supported by the Medical Research Council (UK) grant MR/L010011/1 and the Intramural Research Program at the National Institute on Drug Abuse of the National Institutes of Health. Paired fetal liver and placenta samples were graciously provided by the Joint Medical Research Council/Wellcome Trust (grant number 099175/Z/12/Z) Human Developmental Biology Resource (www.hdbr.org). The online version of this article (doi:10.1007/s11419-017-0389-2) contains supplementary material, which is available to authorized users.Peer reviewedPostprin

Liver cell therapy: is this the end of the beginning?

The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration

Supplementary materials from Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells

Supplementary methods, figures and table