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

Lookup NU author(s): Dr Olivier Govaere

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Abstract

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, hepatic differentiated hSKP [hSKP-derived hepatic progenitor cells (hSKP-HPC)] express hepatic progenitor cell markers (EPCAM, NCAM2, PROM1) and adult hepatocyte markers (ALB), as well as key biotransformation enzymes (CYP1B1, FMO1, GSTA4, GSTM3) and influx and efflux drug transporters (ABCC4, ABCA1, SLC2A5). Using a toxicogenomics approach, we could demonstrate that hSKP-HPC respond to acetaminophen exposure in a comparable way to primary human hepatocytes in culture. The toxicological responses "liver damage", "liver proliferation", "liver necrosis" and "liver steatosis" were found to be significantly enriched in both in vitro models. Also genes associated with either cytotoxic responses or induction of apoptosis (BCL2L11, FOS, HMOX1, TIMP3, and AHR) were commonly upregulated and might represent future molecular biomarkers for hepatotoxicity. In conclusion, our data gives a first indication that hSKP-HPC might represent a suitable preclinical model for in vitro screening of hepatotoxicity. 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. © 2014 Mary Ann Liebert, Inc.


Publication metadata

Author(s): Rodrigues RM, De Kock J, Branson S, Vinken M, Meganathan K, Chaudhari U, Sachinidis A, Govaere O, Roskams T, De Boe V, Vanhaecke T, Rogiers V

Publication type: Article

Publication status: Published

Journal: Stem Cells and Development

Year: 2014

Volume: 23

Issue: 1

Pages: 44-55

Print publication date: 17/08/2013

Online publication date: 21/09/2013

Acceptance date: 01/01/1900

ISSN (print): 1547-3287

ISSN (electronic): 1557-8534

Publisher: Mary Ann Liebert Inc.

URL: https://doi.org/10.1089/scd.2013.0157

DOI: 10.1089/scd.2013.0157

PubMed id: 23952781


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