Rodrigues, Robim M., De Kock, Joery ORCID: 0000-0002-4078-4896, Branson, Steven, Vinken, Mathieu ORCID: 0000-0001-5115-8893, Meganathan, Kesavan, Chaudhari, Umesh ORCID: 0000-0002-7743-4371, Sachinidis, Agapios, Govaere, Olivier ORCID: 0000-0002-4426-6930, Roskams, Tania, De Boe, Veerle, Vanhaecke, Tamara ORCID: 0000-0002-6685-7299 and Rogiers, Vera ORCID: 0000-0003-0635-7740 (2014). Human Skin-Derived Stem Cells as a Novel Cell Source for In Vitro Hepatotoxicity Screening of Pharmaceuticals. Stem Cells Dev., 23 (1). S. 44 - 56. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-8534

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rodrigues, Robim M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Kock, JoeryUNSPECIFIEDorcid.org/0000-0002-4078-4896UNSPECIFIED
Branson, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vinken, MathieuUNSPECIFIEDorcid.org/0000-0001-5115-8893UNSPECIFIED
Meganathan, KesavanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chaudhari, UmeshUNSPECIFIEDorcid.org/0000-0002-7743-4371UNSPECIFIED
Sachinidis, AgapiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Govaere, OlivierUNSPECIFIEDorcid.org/0000-0002-4426-6930UNSPECIFIED
Roskams, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Boe, VeerleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vanhaecke, TamaraUNSPECIFIEDorcid.org/0000-0002-6685-7299UNSPECIFIED
Rogiers, VeraUNSPECIFIEDorcid.org/0000-0003-0635-7740UNSPECIFIED
URN: urn:nbn:de:hbz:38-452732
DOI: 10.1089/scd.2013.0157
Journal or Publication Title: Stem Cells Dev.
Volume: 23
Number: 1
Page Range: S. 44 - 56
Date: 2014
Publisher: MARY ANN LIEBERT, INC
Place of Publication: NEW ROCHELLE
ISSN: 1557-8534
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEPATOCYTE-LIKE CELLS; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; HEPATIC DRUG ELIMINATION; INDUCED LIVER-INJURY; PRECURSOR CELLS; PROMOTES APOPTOSIS; EXPRESSION; TOXICITY; RAT; TOXICOGENOMICSMultiple languages
Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; TransplantationMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/45273

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