Join FCDI at SOT 2019 in Baltimore! With more than 100 Featured and Scientific Sessions and 2,100 individual presentations, the SOT Annual Meeting covers basic and cutting-edge science in dozens of toxicological subdisciplines and provides a wealth of information for all career levels, from students to advanced-career toxicologists. See the SOT website for details on the full 2019 program.
Come visit us in the ToxExpo at Booth #: 3115.
Plan to Attend These Exhibitor-Hosted Sessions
Monday, Mar 11 | 9:00 – 10:00 am | CC Room 340
hiPSC-CMs in Safety and Toxicity Testing—Diversity, Disease Modeling, and Resolving the Reversed Rate Effect of Calcium Channel Blockers
Presented By: T.K. Feaster, FUJIFILM Cellular Dynamics, Inc. and Haoyu Zeng, Merck
Abstract: Experts in the field will discuss a comparative analysis of the effects of cardio-oncology compounds on hiPSC-CMs from multiple donors and show characterization data from several disease models. A mechanistic basis will also be provided to elucidate the increased beat rate phenomenon observed with calcium channel blockers.
Monday, Mar 11 | 12:00 – 1:00 pm | CC Room 338
The Utility of Electrical Field Stimulation for Functional Maturation of hiPSC-CM and Assessment of Inotropic Compounds
Presented By: Xiaoyu Zhang, ACEA Biosciences, Inc. and T.K. Feaster, FUJIFILM Cellular Dynamics, Inc.
Abstract: One of the biggest gaps to full utilization of hiPSC-CM is their inherent maturation status. We discuss the launch of a high-throughput instrument that uses electrical conditioning to achieve fully functional, mature cardiomyocytes, used to assess excitation-contraction coupling and more. We discuss how the system can provide incisive multiparametric and predictive information for safety assessment, drug discovery, and disease modeling.
Tuesday, Mar 12 | 1:30 – 2:30 pm | CC Room 337
Identify Functional and Structural Cardiotoxicants with the Biomarker-Based Cardio quickPredict Assay
Presented By: Jessica Palmer, Stemina Biomarker Discovery
Platform Session: Cardiovascular Toxicology/Hemodynamics
Abstract 3282 | Thursday, Mar 14 | 8:30 – 11:15 am | CC Ballroom I
Predicting Tyrosine Kinase Inhibitor Cardiotoxicity with a Biomarker-Based Human iPSC-Derived Cardiomyocyte Assay
Speaker: Jessica Palmer, Stemina Biomarker Discovery
Platform Session: Cardiovascular Toxicology/Hemodynamics
Abstract 3283 | Thursday, Mar 14 | 8:30 – 11:15 am | CC Ballroom I
Prediction of Liabilities with Chronic Drug Treatment in iPSC Derived Cardiomyocytes Using an MEA Platform
Speaker: C.J. Strock, Cyprotex
Posters Presentations at SOT 2019
Monday, Mar 11 | 9:15 am – 4:30 pm | CC Exhibit Hall
Abstract 1444 | Poster 513
Authors: David Majewski, Jing Liu, Souameng Lor, Tromondae K. Feaster, Simon Hilcove, and Eugenia Jones
FUJIFILM Cellular Dynamics, Inc.
Abstract: Human cell types differentiated from induced pluripotent stem cells (hiPSC) offer a unique access to human cellular material for safety and toxicity screening. Here, we present data demonstrating the utility of hiPSC-derived cardiomyocytes (hiPSC-CMs) in safety assessment and disease modeling. We include a comparative assessment of cancer therapeutics-related cardiac dysfunction (CTRCD) compounds doxorubicin (type I) and sunitinib (type II) across hiPSC-CMs derived from 6 healthy donors (DIV 14) at three concentrations [0.1, 1.0, and 10 µM]. Clinically type I CTRCD may be associated with cellular death, structural changes, and permanent damage while type II CTRCD may be associated with cellular dysfunction, no structural changes, and reversible damage. Here, we identify both type I and type II CTRCD using a selected in-vitro cohort of hiPSC-CMs. These data further provide additional insight into sensitivities to cancer therapeutics across different donors. In addition, we elucidate basic characterization data and pharmacological response for several hiPSC-CM disease models including hypertrophic cardiomyopathy MYH7 (R403Q), LMNA-related dilated cardiomyopathy LMNA (L35P), and brugada syndrome type 3 CACNA1C (G490R) each with its respective isogenic control at DIV 14. We further identify the functional consequences of each mutation and demonstrate that each model recapitulates classical hallmarks of the disease. These data illustrate how hiPSC-CMs provide an excellent model system for assessing compound effects across multiple donors and disease models. Taken together, these examples should help to create new avenues for safety liability assessment and toxicology studies, as well as serve as a template for future opportunities in disease modeling with hiPSC-CMs.
Abstract 1268 | Poster 297
Authors: Reddinger1, Kristin M. Bircsak1, Richard DeBiasio2, Mark Miedel2, Karlijn Wilschut1, Katherine Czysz3, Lawrence Vernetti2, D. Lansing Taylor2, Paul Vulto1, Albert Gough2, and Anthony D. Saleh1
- Mimetas BV
- University of Pittsburgh Drug Discovery Institute
- FUJIFILM Cellular Dynamics International
Abstract: Hepatic injury accounts for two-thirds of drug development failures in the pharmaceutical industry. The current regulatory-accepted models for assessing hepatotoxicity include rodent models which are expensive, low-throughput and overall have unreliable concordance with human hepatotoxicity, as well as standard two-dimensional (2D) in vitro systems (liver cancer cell lines and primary human hepatocytes), which have only marginally improved predictivity. This study sought to optimize a 3D in vitro model of the human liver and predictive hepatoxicity assays by adapting the vascularized Liver Acinus MicroPhysiology System (vLAMPS) developed by the University of Pittsburgh Drug Discovery Institute into MIMETAS’ high-throughput organ-on-a-chip platform. Extracellular matrix (ECM) gels can be contained in the microchambers of the OrganoPlate® through the use of capillary pressure barriers (PhaseGuides™), allowing for solid tissue and barrier formation, as well as perfused tubular endothelial vessel structures to be grown in the medium perfusion channel. The resulting platform contains 96 x 3D microfluidic co-culture biomimetics of the liver sinusoid including FUJIFILM Cellular Dynamics International (CDI) induced pluripotent stem cell-derived hepatocytes (iPSC hepatocytes; iCell Hepatocytes 2.0) and stellate cells incorporated in an ECM protein gel, fed by microfluidic nutrient perfusion from an adjacent endothelial and Kupffer cell-lined blood vessel mimic. Viability of the co-culture remained stable (80-95%) for up to 21 days of culture. We report long-term maintenance of metabolic activity including CYP3A4, as well as albumin and urea production (1-21 days, both up to 20 µg/day/106 cells). Further, we report a significant drop in AFP production over the 21 day culture, as a key indicator of iPSC hepatocyte maturation in the OrganoPlate co-culture that is not observed in standard 2D and 3D culture of these cells. Using multi-parameter high-content imaging, we have optimized toxicity assays with fluorescent readouts to measure viability, mitochondrial function, and steatosis following the administration of known hepatotoxicants, including acetaminophen (APAP). The cell viability assay revealed up to an 80% reduction in the viability of APAP treated OrganoPlate cultures while 2D cultures were unaffected by the same concentration of the hepatotoxicant. These studies display the feasibility of using our iPSC-derived 3D human liver model as a high-throughput screening platform for the assessment of pharmaceutical and environmental hepatotoxicity.
Evaluating the Effects of the Muscarinic Receptor Agonist Pilocarpine on Neural Network Activity Using Three Cell Types on Different Days In Vitro on a Microelectrode Array Platform
Tuesday, Mar 12 | 9:15 am – 4:30 pm | CC Exhibit Hall
The Multi-kinase Inhibitor, C374, Perturbs Excitation-Contraction Coupling in Human iPSC-Derived Cardiomyocytes
Author: VAST Pharma, Gilead Sciences, and Clyde Biosciences
Comparative Gene Expression Profiles of Human Ventricles and the Next Generation In Vitro Human Cardiac Model, Biowire II
Author: Tara Biosystems
Simultaneous Impedance and Field Potential Measurements of hiPSC-Cardiomyocytes for Drug-Induced Cardiotoxicity Prediction
Author: Bristol-Myers Squibb
Thursday, Mar 14 | 8:30 – 11:30 am | CC Hall A
Distinct Carbon Sources Determine the Response of Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Hypoxia
Author: Charles Rivers Laboratories