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
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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