Bioreactor Resources at The Hamner Institutes for Health Sciences Technology Dynamic 3D hepatocyte culture in alginate beads for metabolism and toxicity testing • Long term viability with sustained liver-like functions • Maintaining metabolic capacity over week or more • Computational fluid dynamic modeling to achieve optimal design of the culture system • Biokinetic modeling for in vitro to in vivo extrapolation to predict human clearance and metabolism Liver bioreactor as an in vitro metabolism system • • • • 3D alginate culture in flow-based dynamic culture device (liver bioreactor) Generating in vivo-metabolites in large quantity Enabling the estimation of in vivo clearance for low-clearance compounds In-house designed bioreactors and Quasi-Vivo® cell culture chambers by collaboration with Kirstall Ltd and Parker Co. Parker Hannifin Corporation Applications High-throughput Metabolite Identification • Rapid metabolite identification assisted with in silico modeling software such as Mass-MetaSite™ • Predicting metabolite(s)-mediated toxicity in combination of in silico prediction of bioactivity such as OECD ToolBox • Collaboration with Agilent Technologies Bonn et al, Rapid Commun. Mass Spectrom. 2010; 24: 3127–3138 The Hamner Institutes for Health Sciences www.thehamner.org Applications (continued) Human-on-a-plate - Integrated Multiple Organ Culture Plates for Systemic Toxicity Testing • 3D alginate hepatocyte culture within the plate or liver bioreactor connected to the plate to provide realistic exposure profiles of the parent and metabolites mixture to the target cells About The Hamner • Predicting systemic toxicity in vitro • Collaboration with IonTox, LLC J. McKim, IonTox, LLC Drug-induced Liver Injury and Liver Disease Prediction • Streamlining metabolism and hepatotoxicity testing • As part of Comprehensive Center for Liver and Metabolic Diseases (CCLMDR) consortium References 2015 SOT: Abstract #451, Poster #138 Liver Bioreactor As an In Vitro Metabolism System for Quantitative In Vitro-to-In Vivo Extrapolation. J. M. Pedersen1, J. Shim1, E. LeCluyse1, J. M. Macdonald2,1, M. E. Andersen1, H. J. Clewell1, and M. Yoon1. 1The Hamner Institutes of Health Sciences, Research Triangle Park, NC; and 2University of North Carolina, Chapel Hill, NC. The Hamner Institutes for Health Sciences is an independent, nonprofit organization that offers an open, collaborative and cross-disciplinary approach to translational biomedical research. Based in Research Triangle Park, North Carolina, The Hamner strives to act as a catalyst with global academic institutions, industries, and government to support innovative research and rapid technology development. Novel technologies used at The Hamner include genomic and bioinformatic approaches for improving toxicity testing, in silico models for predictive toxicology, in vitro models that utilize human cells or cell lines to evaluate perturbations of cellular responses, and in vivo models to elucidate genes that play a role in susceptibility to druginduced toxicities. Over the past 37 years, Hamner scientists have been recognized worldwide for their research contributions and training programs in environmental health sciences and chemical risk assessment. 2015 SOT: Abstract #709, Poster #563 Dynamic Flow Models of Tissue Bioreactors for 3D Hepatocyte Culture. J. Shim1, J. M. Pedersen1, J. D. Schroeter2, J. M. Macdonald3, M. E. Andersen1, H. J. Clewell1, and M. Yoon1. 1The Hamner Institutes for Health Sciences, Research Triangle Park, NC; 2Applied Research Associates, Inc., Raleigh, NC; and 3University of North Carolina, Chapel Hill, NC. The Hamner Institutes for Health Sciences 6 Davis Drive PO Box 12137 Research Triangle Park, NC 27709 Phone (919) 558-1200 Fax (919) 558-1400 www.thehamner.org
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