Building Implantable Human Liver Tissue fromPluripotent S tem Cells

Liver disease represents an increasing cause of global morbidityand mortality. Currently, liver transplant is the only treatmentcurative for end s tage liver disease. Donor organs cannot meetthe demand and therefore, scalable treatments and new diseasemodels are required to improve clinical intervention.Pluripotent s tem cells represent a renewable source of humantissue. Recent advances in three-dimensional cell culture hasprovided the field with more complex sys tems that better mimicliver physiology and function. Despite these improvements,current cell-based models are highly variable in performanceand expensive to manufacture at scale. This is due, in part, tothe use of poorly defined or cross-species materials within theprocess, severely affecting technology translation. To addressthis issue, we have developed an automated and economicalplatform to produce liver tissue at scale for modelling diseaseand small molecule screening. S tem cell derived liver spheres were formed by combining hepatic progenitors with endothelialcells and s tellate cells, in the ratios found within the liver. Theresulting tissue permitted the s tudy of human liver biology ‘inthe dish ‘and could be scaled to levels that may prove useful tosupporting failing liver function in humans.