Abstract
Thoracic aortic aneurysm (TAA) denotes a progressive enlargement of the thoracic aorta, entailing a significant risk for life-threatening aortic dissection and/or rupture. At present, mouse models are often used to investigate and therapeutically target the molecular defects underlying TAA, as native aortic samples of patients and, especially, control individuals are hard to collect. Yet, murine in vivo studies are often lengthy and drug testing results did previously not always recapitulate in patients. With the advent of induced pluripotent stem cells (iPSCs), the field is closing in on apt solutions to faithfully model patient and control aortas in a dish. The currently available vascular smooth muscle cell (VSMC) or endothelial cell (EC) monocultures are still overly simplified, as they fail to adequately replicate the complex multilayered and multicellular structure of the aorta. Taking advantage of available iPSCs from syndromic TAA patients (FBN1 & IPO8), my project aims to 1) develop and consolidate the validity of the first iPSC-derived TAA aorta-on-a-chip models, comprising the two VSMC subtypes populating the native ascending aorta along with a layer of arterial ECs, and 2) use the established model to further investigate the disease mechanisms underlying the relatively unexplored IPO8 syndrome. The anticipated outcomes will contribute to the replacement of mouse models (3R principle) and expedite pathophysiological TAA research and drug discovery.
Researcher(s)
Research team(s)
Project type(s)