The Human Induced Pluripotent Stem Cell Test as an Alternative Method for Embryotoxicity Testing.
CardioVision
cardiomyocytes
developmental toxicity
embryotoxicity
hiPS Test
hiPSC
in vitro
video analyses
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Mar 2022
18 Mar 2022
Historique:
received:
09
02
2022
revised:
11
03
2022
accepted:
15
03
2022
entrez:
25
3
2022
pubmed:
26
3
2022
medline:
9
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35328717
pii: ijms23063295
doi: 10.3390/ijms23063295
pmc: PMC8950674
pii:
doi:
Substances chimiques
Teratogens
0
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministry for Culture and Science of the State of North-Rhine Westphalia, Germany
ID : 233-1.08.03.03-121972/131 - 1.08.03.03 - 121972
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