Hepatocytes are well established tools for the drug discovery process, but also find application in disease modeling and therapy. Primary hepatocytes are incorporated into extracorporeal devices called “bioartificial liver” to support patients’ liver function at end-stage liver disease when the organ transplantation is vitally required. Finally, adult hepatocytes have been used in cell therapy of inherited metabolic disorders and a variety of acute and chronic liver pathologies. The supply of primary hepatocytes to support the abovementioned applications is limited, quality is mixed and the alternatives on offer for drug discovery and disease modelling suffer from limitations such as incomplete function, inconsistencies in metabolism and inappropriate genotypes.
We have developed an efficient method of generating hepatocytes from human pluripotent stem cells using a small molecule-driven approach, which does not require the use of growth factors to direct differentiation. The differentiated cells demonstrate end point gene expression, morphology and functionality comparable to primary hepatocytes (the gold standard). The differentiation level is at 90%, which is comparable with what has been described for the most effective GF-based method. The method has also been shown to work with multiple lines of both human embryonic stem cell and human induced pluripotent stem cell origin.
An international patent application protecting the invention has been filed.