Galanjuk, Saskia, Zuehr, Etta, Doenmez, Arif, Bartsch, Deniz, Kurian, Leo, Tigges, Julia and Fritsche, Ellen (2022). The Human Induced Pluripotent Stem Cell Test as an Alternative Method for Embryotoxicity Testing. Int. J. Mol. Sci., 23 (6). BASEL: MDPI. ISSN 1422-0067

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Abstract

The evaluation of substances for their potency to induce embryotoxicity is controlled by safety regulations. Test guidelines for reproductive and developmental toxicity rely mainly on animal studies, which make up the majority of animal usage in regulatory toxicology. Therefore, there is an urgent need for alternative in vitro methods to follow the 3R principles. To improve human safety, cell models based on human cells are of great interest to overcome species differences. Here, human induced pluripotent stem cells (hiPSCs) are an ideal cell source as they largely recapitulate embryonic stem cells without bearing ethical concerns and they are able to differentiate into most cell types of the human body. Here, we set up and characterized a fetal bovine serum (FBS)-free hiPSC-based in vitro test method, called the human induced pluripotent stem cell test (hiPS Test), to evaluate the embryotoxic potential of substances. After 10 days in culture, hiPSCs develop into beating cardiomyocytes. As terminal endpoint evaluations, cell viability, qPCR analyses as well as beating frequency and area of beating cardiomyocytes by video analyses are measured. The embryotoxic positive and non-embryotoxic negative controls, 5-Fluorouracil (5-FU) and Penicillin G (PenG), respectively, were correctly assessed in the hiPS Test. More compounds need to be screened in the future for defining the assay's applicability domain, which will inform us of the suitability of the hiPS Test for detecting adverse effects of substances on embryonic development.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Galanjuk, SaskiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zuehr, EttaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doenmez, ArifUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartsch, DenizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurian, LeoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tigges, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritsche, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-673339
DOI: 10.3390/ijms23063295
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 23
Number: 6
Date: 2022
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IN-VITRO; DEVELOPMENTAL TOXICITY; GENE-EXPRESSION; CULTURE PRACTICE; KEY REGULATOR; PENICILLIN-G; DIFFERENTIATION; 5-FLUOROURACIL; PREDICT; MESP1Multiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67333

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