Engineering Micropatterned Co-cultures for Drug Development

Date: January 21 2016
Presenter(s): Dr. Salman Khetani

Webinar was presented on January 21st, 2016 by Dr. Salman Khetani, Associate Professor, Department of Bioengineering, University of Illinois at Chicago, USA

Summary of the presentation

Due to significant differences across species in liver pathways, models of the human liver are used to screen for potential efficacy and/or toxicity of candidate compounds. Such models serve to complement and reduce the number of animals used in studies required by regulatory agencies. However, once isolated from the liver’s microenvironment, primary hepatocytes rapidly (hours to days) lose phenotypic functions under culture formats that rely exclusively on homogenous extracellular matrix (i.e. collagen) manipulations.

The liver microenvironment in vivo is more complex with cues such as diverse extracellular matrices, tight interactions between hepatocytes and stromal cells, and a precise cellular organization (i.e. architecture). Here, I will discuss our use of semiconductor-driven microfabrication tools and co-culture techniques for building a high fidelity and miniaturized liver model called micropatterned co-cultures (MPCCs). In particular, design principles underlying the development of MPCCs will be discussed followed by functional characterization data sets that have been acquired on MPCCs created using hepatocytes from both human and animal sources.

Finally, I will discuss emerging applications of MPCCs and their continued evolution into predicting clinical outcomes with greater sensitivity. In the future, engineered human liver platforms can significantly reduce drug attrition to lower the cost of drug development and prevent harm to patients in the clinic.

Dr. Khetani received his BS degrees, summa cum laude, in electrical engineering and biomedical engineering from Marquette University, and MS and PhD degrees in bioengineering from the University of California at San Diego (UCSD). He was a Jacobs fellow and National Science Foundation graduate fellow at UCSD. Dr. Khetani conducted his postdoctoral studies at MIT in the laboratory of Dr. Sangeeta Bhatia, professor in the Harvard-MIT Division of Health Sciences and Technology and a world-renowned leader in multi-scale liver tissue engineering and regenerative medicine. Dr. Khetani’s research has been published in peer-reviewed journals such as Drug Metabolism and Disposition, Toxicological Sciences, Nature Biotechnology and the Proceedings of the National Academy of Sciences. In 2007, Dr. Khetani co-founded Hepregen Corporation and led research there as director of research from 2008 to 2011 in order to bring to market bioengineered models of animal and human livers for pharmaceutical drug development. Dr. Khetani then started his academic faculty career in the department of mechanical engineering and school of biomedical engineering at Colorado State University (2011-2015) and recently transitioned as associate professor of bioengineering to University of Illinois at Chicago where he directs the Microfabricated Tissue Models laboratory. He is the recipient of the NSF CAREER award, and his research (past and current) has been funded by DOD, FDA, NIH, NSF, the State of Colorado, and major pharmaceutical companies.