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SELECTBIO Conferences Organ-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions "Track A"


Human Microphysiological Systems for Disease Modeling

George Truskey, R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, Duke University

Human microphysiological systems that use cells from individuals with a range of disease can address limitations of existing animal models that incompletely replicate the disease phenotype.  We have cultured primary and induced pluripotent stem (iPS) cells to model features of a genetic disease, Hutchison-Gilford Progeria Syndrome (HGPS), a rare, accelerated aging disorder caused by an altered form of the lamin A (LMNA) gene termed progerin, exhibited expression of progerin.  Smooth muscle cells and endothelial cells differentiated from iPS cells maintained key features of the mature phenotype for a number of passages. Cells derived from patients with HGPS showed reduced growth rate and increased cell death.  Since the major cause of death in HGPS arises from accelerated atherosclerosis, we developed an arteriole-scale endothelialized  tissue engineered blood vessel (TEBV) with inner diameter of 800 ┬Ám.  eTEBVs fabricated with smooth muscle cells from individuals with HGPS show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis in comparison to eTEBVs fabricated with smooth muscle cells from normal individuals or primary MSCs.  Both the endothelium and smooth muscle cells contributed to disease pathology.  Treatment with a number of compounds being considered for clinical trials reversed the disease progression and improved  the cellular content and function of the eTEBVs.  These results indicate that iPS cells can  be differentiated   to a functional vascular cells and that human eTEBVs can be used to model diseases in vitro.  This approach has been applied to other disease models.

Add to Calendar ▼2018-10-04 00:00:002018-10-05 00:00:00Europe/LondonOrgan-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions "Track A"