Improvement of the embryonic stem cell test endpoint analysis by use of field potential detection
スポンサーリンク
概要
- 論文の詳細を見る
The embryonic stem cell test (EST) is a validated in vitro method to assess the embryotoxic potential of compounds and is a promising tool for drug screening. EST requires microscopic observation of beating cardiomyocytes differentiated from embryonic stem cells as a toxicological endpoint. However, this process is time-consuming and lacks throughput performance. To improve the analysis, we introduced an electrophysiological method with a microelectrode array system for the evaluation of differentiated cardiomyocytes. Embryotoxic (valproic acid, verapamil, and 5-fluorouracil) and non-embryotoxic (penicillin G, d-camphor, and isoniazid) compounds were assessed with the system. Mouse embryonic stem cells were differentiated into cardiomyocytes and treated with each compound during the differentiation process. The embryotoxicity of each compound was then assessed by measuring the field potentials of differentiated cardiomyocytes using the microelectrode array system, as well as by microscopic evaluation. All the embryotoxic compounds dose-dependently inhibited the field potential formation and the myocardial beating of differentiated cells, while the non-embryotoxic compounds did not affect either endpoint. The detection capabilities of the two assay methods were similar. These results indicated that the field potential measurements can be used as an alternative endpoint of EST. Moreover, the field potential can be measured automatically, introducing a high throughput performance compared to the conventional microscopic observation. We therefore concluded that the endpoint analysis with the microelectrode array system improves the original EST and can be useful for the assessment of the embryotoxic potential of compounds.
著者
-
Funabashi Hitoshi
Safety Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd.
-
Seki Takaki
Safety Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd.
-
KOSEKI Naoteru
Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
-
DEGUCHI Jiro
Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
-
YAMADA Toru
Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
関連論文
- The First Case of Feline Infectious Peritonitis-like Pyogranuloma in a Ferret Infected by Coronavirus in Japan
- Influences of biofluid sample collection and handling procedures on GC-MS based metabolomic studies(METHODS)
- Improvement of the embryonic stem cell test endpoint analysis by use of field potential detection
- Improvement of the embryonic stem cell test endpoint analysis by use of field potential detection
- Application of Prohibitin Immunohistochemistry to Rat Livers Treated with Methapyrilene Hydrochloride
- Relationship between liver weight change and gene expression of hepatic cytochrome P450 isoforms in clobazam-treated rats(Proceedings of the 32nd Annual Meeting)
- Usefulness of field potential as a marker of embryonic stem cell-derived cardiomyocytes, and endpoint analysis of embryonic stem cell test
- Spontaneous Fibrosarcoma with Pleomorphic Appearance in an Aged Brown Norway Rat
- Application of Prohibitin Immunohistochemistry to Rat Livers Treated with Methapyrilene Hydrochloride
- Assessment of technical protocols for novel embryonic stem cell tests with molecular markers (Hand1- and Cmya1-ESTs) : a preliminary cross-laboratory performance analysis