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SELECTBIO Conferences 3D-Culture, Organoids & Organ-on-a-Chip Europe 2021

David Hay's Biography

David Hay, Principal Investigator/RCUK Fellow, MRC Centre for Regenerative Medicine

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Modeling Human Fatty Liver Disease Using Stem Cell-derived Liver Tissue

Tuesday, 29 June 2021 at 11:00

Add to Calendar ▼2021-06-29 11:00:002021-06-29 12:00:00Europe/LondonModeling Human Fatty Liver Disease Using Stem Cell-derived Liver Tissue3D-Culture, Organoids and Organ-on-a-Chip Europe 2021 in Rotterdam, The NetherlandsRotterdam, The

Liver disease represents an increasing cause of global morbidity and mortality. Although liver transplant is a curative treatment for end stage liver disease, donor organs cannot meet the demand. Therefore, scalable treatments and new disease models are required to improve clinical intervention.  A major contributor to liver disease worldwide is obesity. This has led to a surge in fatty liver disease. This term encompasses a spectrum of pathologies, ranging from benign hepatic steatosis to disease initiating non-alcoholic steatohepatitis. Although there are a number of in vitro approaches for the study of fatty liver disease, they do possess drawbacks. For example, cell line based models display perturbed metabolic function, arising from malignant transformation and immortalization. Alternatively, primary mouse and human hepatocytes can be used to model hepatic steatosis in vitro; however, those systems display unstable phenotype post isolation, limiting their application. Moreover, human hepatocytes are commonly isolated from transplant-rejected organs, often fatty livers, which may adversely affect model performance. In contrast to this, pluripotent stem cell derived systems represent a renewable source of human tissue to model disease and physiology. Most recently, we have used our human liver models to study hepatic steatosis, providing insight into the disease process. Those studies revealed that steatotic liver tissue displayed a compromised electron transport chain as well as a truncated TCA cycle. The steatotic hepatocytes rewired their metabolic circuitry to compensate for this, generating increased levels of fumarate through the purine nucleotide cycle, and to a lesser extent the malate-aspartate shuttle. We are currently developing those models to probe other aspects of fatty liver disease and our most recent studies will be presented at the meeting.

Add to Calendar ▼2021-06-28 00:00:002021-06-30 00:00:00Europe/London3D-Culture, Organoids and Organ-on-a-Chip Europe 20213D-Culture, Organoids and Organ-on-a-Chip Europe 2021 in Rotterdam, The NetherlandsRotterdam, The