Engineered Multi-Tissue Platform for Modeling Systemic Human Pathologies

Friday, October 2, 2020 -
2:00pm to 3:00pm
Zoom
Kacey Ronaldson-Bouchard

Associate Research Scientist
Laboratory for Stem Cells and Tissue Engineering
Department of Biomedical Engineering
Columbia University

Engineered Multi-Tissue Platform for Modeling Systemic Human Pathologies

Abstract: 

Bioengineered tissue platforms offer a new paradigm for modeling human pathophysiology and testing drug efficacy and safety. At present, establishing physiological communication between multiple tissues while preserving their individual phenotypes remains a major challenge that must be overcome to model whole-body physiology and systemic diseases. Toward this goal, we developed the biomimetic InterOrgan platform in which matured human tissues are connected in a way that allows maintaining distinct functionalities of different organs (e.g. heart, liver, bone, skin). Each tissue is cultured in its own optimized environment and separated from the recirculating vascular flow containing monocytes, by a matured and selectively permeable endothelial barrier. Tissues linked by vascular perfusion maintained their molecular, structural, and functional phenotypes over four weeks of culture, recapitulated multi-organ toxicity of doxorubicin observed in pediatric and adult clinical studies, and enabled identification of clinically relevant early miRNA biomarkers of cardiotoxicity. Additionally, the platform shows utility for immune-oncology applications as circulating tumor cells preferentially extravasate to expected metastatic sites and myocardial cryoinjury studies demonstrate immune infiltration to the site of injury. Overall, the InterOrgan platform can facilitate clinical translation by enabling physiologic communication of phenotypically stable engineered human tissues.

 

Bio: 

Dr. Kacey Ronaldson-Bouchard is an Associate Research Scientist at Columbia University’s Department of Biomedical Engineering in New York City. She received her Ph.D. at Columbia in 2015 under the advisement of Dr. Gordana Vunjak-Novakovic. Her research focuses on engineering multicellular systems from pluripotent stem cells, including the advanced maturation of iPSC-derived cardiomyocytes into mature, functional cardiac microtissues. In addition, Dr. Ronaldson-Bouchard has an interest in integrating multiple engineered tissue models for studying inter-organ interactions, towards the development of patient avatar models for the realization of personalized medicine. She has published peer-reviewed articles in journals including Nature, Cell Stem Cell, and Cell, and is a co-founder of TARA Biosystems, a NYC-based startup company focused on engineering advanced cardiac models for drug discovery, testing, and precision cardiology.