ALDH1A1 expression can be detected in canals of Hering and bile duct epithelial cells STA-9090 research buy and is increased on liver injury. Finally, we showed that the isolation and differentiation toward hepatocyte-like cells of LPCs with high ALDH activity is also successfully applicable to human liver samples. Conclusion: High ALDH activity is a feature of LPCs that
can be taken advantage of to isolate these cells from untreated mouse as well as human liver tissues. This novel protocol is practically relevant, because it provides an easy and nontoxic method to isolate liver stem cells from normal tissue for potential therapeutic purposes. (HEPATOLOGY 2012) Functional hepatocyte cultures are a crucial tool in the development of new therapeutic agents, providing the best available surrogate for liver toxicity
testing. In addition, transplantation of freshly isolated human hepatocytes can be a cellular source for hepatic parenchymal replacement therapy, because the number of needed donor organs exceeds the demand. Additionally, for certain liver diseases even a partial correction of gene function can be curative, and thus a complete liver transplantation is not always necessary.1, 2 The major limiting factor in these applications is the availability of sufficient good-quality selleck chemicals hepatocytes. One of the promising properties of stem cells is their potential to provide a renewable source of hepatocytes.3 From this perspective, much is expected from the use of embryonic stem cells, their induced counterparts, and liver progenitor cells (LPCs).4 LPCs are bipotential stem cells present in low numbers in several different niches in the healthy liver.5 When hepatocytes are overwhelmed by the severity of an injury, these LPCs expand and replenish the liver with new hepatocytes.6 The isolation and characterization of LPCs has been the subject of many studies aiming at a better understanding of LPC biology to apply in the generation
of high-quality hepatocytes for toxicology studies, improving liver regeneration, or even to serve as a source for direct transplantation after liver injury. Techniques for isolation of LPCs are often a combination of gradient centrifugation methods with cell separation Masitinib (AB1010) techniques like fluorescence-activated cell sorting (FACS) or magnetic activated cell separation using antibodies against various stem cell markers.7-10 Functions attributed to stem cells have also been used for their enrichment, e.g., telomerase activity,11 selective attachment on matrices,12 resistance to hypoxia,13 or the side population technique, which is based on efflux of Hoechst-33342 through the ATP-binding cassette (ABC) pumps.14 Recently, aldehyde dehydrogenase (ALDH) activity has received considerable attention as a valuable functional strategy for isolating normal and cancerous stem cells from several tumor types.