title: A phenotypic in vitro model for the main determinants of human whole heart function.
abstract: This article details the construction and testing of a phenotypic assay system that models in vivo cardiac function in a parallel in vitro environment with human stem cell derived cardiomyocytes. The major determinants of human whole-heart function were experimentally modeled by integrating separate 2D cellular systems with BioMicroelectromechanical Systems (BioMEMS) constructs. The model features a serum-free defined medium to enable both acute and chronic evaluation of drugs and toxins. The integration of data from both systems produced biologically relevant predictions of cardiac function in response to varying concentrations of selected drugs. Sotalol, norepinephrine and verapamil were shown to affect the measured parameters according to their specific mechanism of action, in agreement with clinical data. This system is applicable for cardiac side effect assessment, general toxicology, efficacy studies, and evaluation of in vitro cellular disease models in body-on-a-chip systems.
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Stancescu
authors.affiliation: Department of Zoology, University of West Hungary, Szombathely H-9700, Hungary; Biomedical Engineering, Cornell University, Department of Biomedical Engineering, 115 Weill Hall, Ithaca, NY 14853, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Molnar
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: McAleer
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
authors.forename: William
authors.initials: W
authors.lastname: McLamb
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Long
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA.
authors.forename: Carlota
authors.initials: C
authors.lastname: Oleaga
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA; Biomedical Engineering, Cornell University, Department of Biomedical Engineering, 115 Weill Hall, Ithaca, NY 14853, USA.
authors.forename: Jean-Matthieu
authors.initials: JM
authors.lastname: Prot
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA. Electronic address: jhickman@mail.ucf.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hickman
mesh_terms: D018929:Cell Culture Techniques / Q000295:instrumentation*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D004867:Equipment Design; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation*; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*
keywords: Cardiomyocyte; Conduction; Force generation; Functional assay; Human; Serum-free