Machine-learning-based quality control of contractility of cultured human-induced pluripotent stem-cell-derived cardiomyocytes.

Journal: Biochemical and biophysical research communications
PMID:

Abstract

The precise and early assessment of cardiotoxicity is fundamental to bring forward novel drug candidates to the pharmaceutical market and to avoid their withdrawal from the market. Recent preclinical studies have attempted to use human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) to predict clinical cardiotoxicity, but the heterogeneity and inconsistency in the functional qualities of the spontaneous contractility of hiPSC-CMs across cell culture wells and product lots still matter. To rapidly assess the functional qualities of hiPSC-CMs without histological labeling, we optically detected the contractility of confluently cultured hiPSC-CMs using bright-field microscopy. Using a method that consisted of data preprocessing, data augmentation, dimensionality reduction, and supervised learning, we succeeded in precisely discriminating between functionally normal and abnormal contractions of hiPSC-CMs.

Authors

  • Ken Orita
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Kohei Sawada
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Nobuyoshi Matsumoto
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Yuji Ikegaya
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; iPS-non Clinical Experiments for Nervous System (iNCENS) Project, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, Osaka 565-0871, Japan. Electronic address: yuji@ikegaya.jp.