Universität zu Köln

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

Full text not available from this repository.

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:	Creators Email ORCID ORCID Put Code Rodrigues, Robim M. UNSPECIFIED UNSPECIFIED UNSPECIFIED De Kock, Joery UNSPECIFIED orcid.org/0000-0002-4078-4896 UNSPECIFIED Branson, Steven UNSPECIFIED UNSPECIFIED UNSPECIFIED Vinken, Mathieu UNSPECIFIED orcid.org/0000-0001-5115-8893 UNSPECIFIED Meganathan, Kesavan UNSPECIFIED UNSPECIFIED UNSPECIFIED Chaudhari, Umesh UNSPECIFIED orcid.org/0000-0002-7743-4371 UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Govaere, Olivier UNSPECIFIED orcid.org/0000-0002-4426-6930 UNSPECIFIED Roskams, Tania UNSPECIFIED UNSPECIFIED UNSPECIFIED De Boe, Veerle UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanhaecke, Tamara UNSPECIFIED orcid.org/0000-0002-6685-7299 UNSPECIFIED Rogiers, Vera UNSPECIFIED orcid.org/0000-0003-0635-7740 UNSPECIFIED
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:	Keywords Language HEPATOCYTE-LIKE CELLS; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; HEPATIC DRUG ELIMINATION; INDUCED LIVER-INJURY; PRECURSOR CELLS; PROMOTES APOPTOSIS; EXPRESSION; TOXICITY; RAT; TOXICOGENOMICS Multiple languages Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45273