In this wory, the scientists used used a combination of lentiviral vectors expressing hepatic fate-conversion factors with Oct4, Sox2,Klf4, and Myc to convert mouse embryonic fibroblasts into hepatic cells ( iHepL cells). When transplanted into partial hepatectomized and hepatic irradiated mice, iHepL cells differentiated into hepatocytes and cholangiocytes. However, iHepL cells formed malignant non-teratoma cell aggregations in one out of five engrafted livers and five out of five xenografts assays. All the cells in these tumors had silenced key hepatic fate-conversion factors, and lost hepatic features.
This study highlights the dangers of using pluripotency factors in reprogramming strategies when fate-conversion factors are silenced in vivo, and urges us to perform extensive tumorigenic tests in reprogrammed cells.
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In this wory, the scientists used used a combination of lentiviral vectors expressing hepatic fate-conversion factors with Oct4, Sox2,Klf4, and Myc to convert mouse embryonic fibroblasts into hepatic cells ( iHepL cells). When transplanted into partial hepatectomized and hepatic irradiated mice, iHepL cells differentiated into hepatocytes and cholangiocytes. However, iHepL cells formed malignant non-teratoma cell aggregations in one out of five engrafted livers and five out of five xenografts assays. All the cells in these tumors had silenced key hepatic fate-conversion factors, and lost hepatic features.
This study highlights the dangers of using pluripotency factors in reprogramming strategies when fate-conversion factors are silenced in vivo, and urges us to perform extensive tumorigenic tests in reprogrammed cells.