Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals.

Human skin-derived precursors (hSKP) are postnatal stem cells with neural crest properties that reside in the dermis of human skin. These cells can be easily isolated from small (fore)skin segments and have the capacity to differentiate into multiple cell types. In this study, we show that upon exposure to hepatogenic growth factors and cytokines, hSKP acquire sufficient hepatic features that could make these cells suitable in vitro tools for hepatotoxicity screening of new chemical entities and already existing pharmaceutical compounds. Indeed, these cells express at the gene level several phase I and phase II biotransformation enzymes as well as influx (phase 0) and efflux (phase III) drug transporters. Moreover, using a toxicogenomics approach, we could demonstrate that the hepatic differentiated hSKP respond to acetaminophen exposure in a comparable way to primary human hepatocytes in culture. Specifically, the toxicological responses 'liver damage', 'liver proliferation', 'liver necrosis' and 'liver steatosis' are present in both in vitro models. To the best of our knowledge, this is the first report in which human postnatal stem cells derived from skin are described as a potentially relevant cell source for in vitro hepatotoxicity testing of pharmaceutical compounds.

Jaar van publicatie:2014

Trefwoorden:Tissue-specific stem cells, Differentiation, human skin-derived precursors