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Promega Corporation

Dr. David C. Hay, MRC Centre for Regenerative Medicine

Generating Metabolically Active Hepatocytes From Pluripotent Stem Cells

Abstract

Faithfully recapitulating human physiology "in a dish" from a renewable source remains a holy grail for medicine and pharma. Many procedures have been described that, to a limited extent, exhibit human tissue specific function in vitro. In particular, incomplete cellular differentiation and/or the loss of cell phenotype post-differentiation play a major part in this void. We have developed an interdisciplinary approach to address this problem, employing skill sets in cell biology, materials chemistry and pharmacology. Our approach yields metabolically active hepatocyte populations that display stable function for over two weeks in vitro. Although metabolic activity is an important indication of cell utility, the accurate prediction of cellular toxicity in response to specific pharmacological compounds represents our goal. Therefore, detailed analysis of hepatocellular toxicity was performed in response to well defined compounds and compared to primary human hepatocytes. Importantly, stem cell derived hepatocytes display equivalence to primary human material. Moreover, we demonstrate that our approach is capable of modelling metabolic differences frequently observed in the population. In conclusion, we report that pluripotent stem cell derived hepatocytes will model toxicity predictably and in a manner comparable to current gold standard assays.

Dr David Hay is a Principal Investigator at the University of Edinburgh’s MRC Centre for Regenerative Medicine. David has worked in the field of stem cell biology and differentiation over the last decade. David’s work has highlighted the important role that biology and chemistry play in generating high fidelity human liver cells from pluripotent stem cells. The impact of this work has led to a number of publications, successful grant applications, a spin-out company, FibromEd, and regular appearances at high profile international conferences.

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