Pluripotent stem cell-derived hepatocytes: potential and challenges in pharmacology.

The liver is a fascinating organ and performs a wide range of functions necessary for life. Because the hepatocyte is the major functional cell type found in the liver, it is important that we better understand its role in health and disease. Functional hepatocytes have been derived from many sources, including human stem cell populations. These models offer new opportunities to further our understanding of human liver biology from diverse genotypes and, in the future, to facilitate the development of novel medicines or cell-based therapies. This review discusses limitations in current cell-based models and the advantages offered by pluripotent stem cell-derived hepatocytes.

Serum Free Production of Three-dimensional Human Hepatospheres from Pluripotent Stem Cells.

The development of renewable sources of liver tissue is required to improve cell-based modelling, and develop human tissue for transplantation. Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) represent promising sources of human liver spheres. We have developed a serum free and defined method of cellular differentiation to generate three-dimensional human liver spheres formed from human pluripotent stem cells. A potential limitation of the technology is the production of dense spheres with dead material inside. In order to circumvent this, we have employed agarose microwell technology at defined cell densities to control the size of the 3D spheres, preventing the generation of apoptotic and/or necrotic cores.  Notably, the spheres generated by our approach display liver function and stable phenotype, representing a valuable resource for basic and applied scientific research. We believe that our approach could be used as a platform technology to develop further tissues to model and treat human disease and in the future may permit the generation of human tissue with complex tissue architecture.