Join us at the ACEA Cardio Symposium held one day prior to the SPS 2018 Annual Meeting in Washington, DC (held at the same venue as SPS 2018). ACEA Biosciences’ annual Cardio Symposium is a forum to promote scientific exchange and collaboration amongst scientists working at the forefront of cardiac safety assessment and cardiovascular disease model research. Experts from both industry and academia will share their findings on combining human induced pluripotent stem cell-derived (hiPSC) cardiomyocytes, cellular impedance, MEA and other technologies for cardiac safety assessment and cardiovascular disease studies.
SPS 2018 Annual Meeting
The 2018 SPS Scientific Program features a diverse range of sessions organized into two themed tracks and covering issues such as Opiates, Secondary Pharmacology, Non-opiate Pain Management, Safety Pharmacology/FDA Discussion on GI, CiPA Real-life Implementation, Cardio GPCR, Cardio-oncology, New Strategies in CNS and Sensory Assessments, Imaging, In Silico, Phase I Trial Design and Translation to Clinical Data, Preclinical to Clinical-Case Studies and much more! This will ensure attendees can stay abreast of new content and developments in key areas of interest. The meeting also offers a broad Continuing Education program both on an introductory level as well as advanced courses for the expert.
Fujifilm Cellular Dynamics Sponsored Presentation
Tuesday, October 2 | 12:30 – 1:30 pm | Hoover Room
Session Title: Implementing Human iPSC-derived Cells in Early Safety Assessment and Disease Modeling
Presented by: Fujifilm Cellular Dynamics, Inc. and Nanion Technologies GmbH
Speakers: T.K. Feaster, PhD, Product Manager, Fujifilm Cellular Dynamics, Inc. and Sonja Stoelzle-Feix, PhD, Director, Scientific Affairs, Nanion Technologies GmbH
Part I: 12:30 – 12:45 pm
Dr. T.K. Feaster will discuss the predictive power of human iPSC-derived cells for in vitro toxicity testing. He will highlight toxicology, drug screening, and disease models. Demonstrating increased functionality and throughput valuable for identifying liabilities early in preclinical safety programs.
Part II: 12:50 – 1:20 pm
Dr. Sonja Stoelzle-Feix will discuss the effects of “CiPA drugs” on excitation-contraction coupling in iCell Cardiomyocytes2. She will describe the evaluation of the proarrhythmic potential of 23 blinded drugs on hiPSC-CMs using iCell Cardiomyocytes2 and the Nanion CardioExcyte 96 at different sites. Ion channel data and myocyte behavior will be discussed and aligned.
Poster Number: 0164 | October 1 – 2, 2018
Evaluation of Hypertrophic Cardiomyopathy Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes Reveals Abnormal Excitation Contraction Coupling
Jing Liu, Souameng Lor, Natsuyo Aoyama, Tromondae K. Feaster, Simon Hilcove, and Eugenia Jones, Fujifilm Cellular Dynamics
Presenter: T.K. Feaster, PhD, Fujifilm Cellular Dynamics
Abstract: Sarcomeric cardiomyopathies, including hypertrophic cardiomyopathy (HCM), are an important cause of morbidity and mortality. Clinically, HCM is characterized by ventricular wall thickening as a result of enlarged cardiomyocytes, preserved ejection fraction concurrent with diastolic dysfunction, and arrhythmias. One of the most common forms of HCM arises from a missense mutation in the gene encoding the beta myosin heavy chain protein (MYH7), resulting in a change of amino acid 403 from arginine-to-glycine (R403Q). A major hindrance to detailed study of sarcomeric cardiomyopathies in humans has been lack of an appropriate in vitro cardiac tissue model. Here, we use human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) to study the functional consequence of the HCM MYH7 R403Q mutation, specifically electrophysiology, calcium handling, and contraction. HiPSC-CMs were generated through reprogramming of somatic cells from a patient carrying the HCM MYH7 R403Q mutation. In addition, we use genome engineering strategies to correct the mutation, creating an isogenic control. Moreover, we developed an induced hypertrophy model by exposing control hiPSC-CMs to endothelin-1 (ET-1). Both inherited and induced models display classic hallmarks of hypertrophy, including up-regulation of fetal genes, cytoskeletal rearrangements, and increased hiPSC-CM size. In addition, the HCM MYH7 R403Q hiPSC-CMs display abnormal electrophysiological properties and calcium handling properties including significantly slower calcium decay rates and prolonged calcium handling kinetics (i.e., time to peak and time to baseline) concurrent with contractile dysfunction. These data illustrate the advantages of disease modeling using hiPSC technology. We conclude that patient-specific hiPSC-CMs exhibit classic clinical phenotypes relative to control. We show that the induced and inherited HCM phenotype hiPSC-CMs have common structural and functional features. In total, hiPSC technology enables a reliable and reproducible disease model not previously attainable and provides new solutions, tools, and opportunities for sarcomeric cardiomyopathy mechanistic elucidation and novel therapeutic research.