Your browser doesn't support javascript.
loading
CSAHi study: Validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes -assessment of inter-facility and cells lot-to-lot-variability.
Nozaki, Yumiko; Honda, Yayoi; Watanabe, Hitoshi; Saiki, Shota; Koyabu, Kiyotaka; Itoh, Tetsuji; Nagasawa, Chiho; Nakamori, Chiaki; Nakayama, Chiaki; Iwasaki, Hiroshi; Suzuki, Shinobu; Washio, Ikumi; Takahashi, Etsushi; Miyamoto, Kaori; Yamanishi, Atsuhiro; Endo, Hiroko; Shinozaki, Junko; Nogawa, Hisashi; Kunimatsu, Takeshi.
Afiliación
  • Nozaki Y; Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
  • Honda Y; Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
  • Watanabe H; Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
  • Saiki S; Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan; Consortium for Safety Assessment Using Human iPS Cells (CSAHi), Japan.
  • Koyabu K; Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
  • Itoh T; Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
  • Nagasawa C; Research Center, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan; Consortium for Safety Assessment Using Human iPS Cells (CSAHi), Japan.
  • Nakamori C; Research Center, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
  • Nakayama C; Research Center, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
  • Iwasaki H; Research Center, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
  • Suzuki S; Nippon Boehringer Ingelheim Co., Ltd., 6-7-5, Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan; Consortium for Safety Assessment Using Human iPS Cells (CSAHi), Japan.
  • Washio I; Nippon Boehringer Ingelheim Co., Ltd., 6-7-5, Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
  • Takahashi E; Research Laboratories, Toyama Chemical Co., Ltd., 4-1, Shimookui 2-chome, Toyama 930-8508, Japan; Consortium for Safety Assessment Using Human iPS Cells (CSAHi), Japan.
  • Miyamoto K; Research Laboratories, Toyama Chemical Co., Ltd., 4-1, Shimookui 2-chome, Toyama 930-8508, Japan.
  • Yamanishi A; Toxicology Research Laboratory, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan; Consortium for Safety Assessment Using Human iPS Cells (CSAHi), Japan.
  • Endo H; Toxicology Research Laboratory, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan.
  • Shinozaki J; Toxicology Research Laboratory, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan.
  • Nogawa H; Toxicology Research Laboratory, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan.
  • Kunimatsu T; Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan; Consortium for Safety Assessment Using Human iPS Cells (CSAHi), Japan; Non-Clinical Evaluation Expert Committee, Drug Evaluation Committee, Japan Pharmaceutical Manufactu
Regul Toxicol Pharmacol ; 77: 75-86, 2016 Jun.
Article en En | MEDLINE | ID: mdl-26884090
In vitro screening of hERG channels are recommended under ICH S7B guidelines to predict drug-induced QT prolongation and Torsade de Pointes (TdP), whereas proarrhythmia is known to be evoked by blockage of other ion channels involved in cardiac contraction and compensation mechanisms. A consortium for drug safety assessment using human iPS cells-derived cardiomyocytes (hiPS-CMs), CSAHi, has been organized to establish a novel in vitro test system that would enable better prediction of drug-induced proarrhythmia and QT prolongation. Here we report the inter-facility and cells lot-to-lot variability evaluated with FPDc (corrected field potential duration), FPDc10 (10% FPDc change concentration), beat rate and incidence of arrhythmia-like waveform or arrest on hiPS-CMs in a multi-electrode array system. Arrhythmia-like waveforms were evident for all test compounds, other than chromanol 293B, that evoked FPDc prolongation in this system and are reported to induce TdP in clinical practice. There was no apparent cells lot-to-lot variability, while inter-facility variabilities were limited within ranges from 3.9- to 20-folds for FPDc10 and about 10-folds for the minimum concentration inducing arrhythmia-like waveform or arrests. In conclusion, the new assay model reported here would enable accurate prediction of a drug potential for proarrhythmia.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arritmias Cardíacas / Diferenciación Celular / Pruebas de Toxicidad / Bloqueadores de los Canales de Potasio / Miocitos Cardíacos / Células Madre Pluripotentes Inducidas / Canal de Potasio ERG1 / Frecuencia Cardíaca / Microelectrodos Tipo de estudio: Clinical_trials / Etiology_studies / Guideline / Prognostic_studies / Risk_factors_studies Límite: Humans País/Región como asunto: Asia Idioma: En Revista: Regul Toxicol Pharmacol Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arritmias Cardíacas / Diferenciación Celular / Pruebas de Toxicidad / Bloqueadores de los Canales de Potasio / Miocitos Cardíacos / Células Madre Pluripotentes Inducidas / Canal de Potasio ERG1 / Frecuencia Cardíaca / Microelectrodos Tipo de estudio: Clinical_trials / Etiology_studies / Guideline / Prognostic_studies / Risk_factors_studies Límite: Humans País/Región como asunto: Asia Idioma: En Revista: Regul Toxicol Pharmacol Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos