Abstract
Stem cell-derived hepatocytes represent promising models to study human liver biology and disease. This concise review discusses the recent progresses in the field, with a focus on human liver disease, drug metabolism and virus infection.
Highlights
The human liver has a multitude of functions
We have developed a highly efficient method to deliver functional hepatocytes which could be assayed in a high throughput format [18]
And in agreement with studies using Human Embryonic Stem Cells (hESCs), there are significant variations in Induced Pluripotent Stem Cells (iPSCs) hepatic differentiation capacity [29]. iPSC clones derived from peripheral blood cells were found to be comparable to dermal fibroblasts from the same individual, but differentiation capacity varied from donor to donor using a modified version of our procedure [18,30]
Summary
The human liver has a multitude of functions. The cells which comprise the liver and perform those roles are termed parenchymal and non-parenchymal. Isolated human primary hepatocytes (PHHs) are recognized as the “gold standard” for evaluating liver metabolism and drug toxicity [4]. Enzyme expression drops off markedly during cell culture which can complicate biological interpretation [5,6] In addition to their instability, PHHs widespread use is limited by their scarcity and quality [7]. To overcome the shortage and stability of PHHs, a number of different human hepatoma-derived cell lines have been established. In contrast to PHHs, hepatoma-derived cells are scalable, cheap to maintain and are easy to handle. Those benefits are out-weighed by defects in key cell signaling pathways which result in inferior phenotype. We believe that this has revolutionary potential for modern medicine (Figure 1) and discuss the potential of stem cells in more detail throughout the review
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