A robust reprogramming strategy for generating hepatocyte-like cells usable in pharmaco-toxicological studies

We have designed and implemented a novel and robust approach to obtain hepatocytes from individuals by direct reprogramming, which is based on a combination of a single doxycycline-inducible polycistronic vector system expressing HNF4A, HNF1A and FOXA3, introduced in human fibroblasts previously transduced with human telomerase reverse transcriptase (hTERT). These cells can be maintained in fibroblast culture media, under standard cell culture conditions. We have analyzed the cell extracts of diHLC-T incubated with reference hepatotoxicants to obtain a predictive model of toxicity caused by drugs