The application of 3D Bioprinted Human Tissues in Disease Modeling & Regenerative Medicine
Guest Speaker: Sharon Collins Presnell
Liver tissues that are constructed in vitro from both parenchymal and non-parenchymal cellular components offer advantages in basic functionality and their ability to be applied broadly to disease modeling and regenerative medicine. Advanced fabrication platforms, such as three-dimensional cellular bioprinting, can enhance the reproducibility and complexity of in vitro-generated tissues. Human liver tissues comprising primary hepatocytes, endothelial cells, and stellate cells have been utilized to model the complex disease phenomena of fatty liver disease (NAFLD/NASH) and fibrosis. In the presence of disease-inducing stimuli such as profibrogenic growth factors, fatty acids, and high sugars, model liver tissues develop hallmark features of progressive NAFLD/NASH, including inflammation, macro- and microvesicular steatosis, fibrogenesis, and hepatocellular ballooning. Key features of these disease-relevant phenotypes can be prevented or modulated by tool compounds known to interfere with disease-associated pathways. Furthermore, the construction of tissues using cells of disease origin reveals that the disease phenotype, in part, is retained within those cellular raw materials and can facilitate the development of disease-like features independent of the presence of exogenous inducers. Models such as these have the potential to be an effective, human-relevant means of screening therapies for the discovery and advancement of new treatment modalities for NASH. For patient populations that have specific liver deficiencies, such as urea cycle deficiencies and alpha-1-antitrypsin deficiency, the implantation of liver tissue patches may offer a clinical solution that overcomes in part the shortage of donor organs available for transplantation. Recent studies have demonstrated that the implantation of bioprinted human liver patches resulted in tissue engraftment and production of human A1AT protein in the background of the piZ A1AT-deficient mouse model, with a ~75% reduction in presence of the misfolded A1AT protein evident in the liver adjacent to the transplanted graft. Taken together, these data support continued investigations into the use of in vitro-engineered human liver tissues for drug discovery and regenerative medicine.
Sharon Collins Presnell, Ph.D., Chief Scientific Officer (Organovo) and President (Samsara Sciences), has more than 17 years of experience in the leadership of product-focused R&D. At the University of North Carolina at Chapel Hill, Dr. Presnell’s research in liver and prostate biology and carcinogenesis produced cell- and tissue-based technologies that were industry-funded or outlicensed for industrial applications. She joined Becton Dickinson (BD) in 2001 and played a key role in the early discovery and development of cell-based tools and reagents for BD's life sciences portfolio. At BD, she grew and led a large multi-disciplinary team to build and validate screening platforms and products for cell growth, differentiation, and characterization and secured revenue-generating commercial partnerships with pharma partners. Sharon joined Tengion, Inc. in 2007, and as the Senior Vice President of Regenerative Medicine Research was responsible for leading the discovery and early development of Tengion’s Neo-Kidney Augment™, a clinical-stage cell-based therapy for patients with chronic kidney disease. As the Chief Technology Officer at Organovo, Dr. Presnell led the growth and development of the R&D organization, including evolution of the company’s technology portfolio, and has played an instrumental role in securing funds in support of corporate growth initiatives. In 2015, she led the establishment of Samsara Sciences, Inc., a wholly-owned subsidiary of Organovo, a company focused on the ethical and comprehensive provision of human cellular reagents for discovery and regenerative medicine applications. She currently serves as the President of Samsara Sciences and the Chief Scientific Officer of Organovo. Sharon holds a Ph.D. in pathology from the Medical College of Virginia. Dr. Presnell is a member of the American Society of Investigative Pathology, the American Society of Nephrology, and the International Society of Cell Transplantation, serves on the editorial board of the journal ‘3D Printing and Additive Manufacturing’, and remains active as an NIH reviewer as an industry representative in the biomedical engineering space.