Aortic stenosis (AS) occurs when one of the heart's valves narrows and blood cannot flow to the rest of the body normally. The disease can range from mild to severe and AS progression is unpredictable often occurring over many years. If severe aortic valve disease is left untreated this can lead to life-threatening problems, such as heart failure. Current treatments are limited to replacement of the faulty valve, ideally before the level of heart damage becomes too severe. However, predicting which patients will benefit from valve replacement and when to intervene is currently challenging due to lack of reliable clinical tools. In this project, we will follow patients before and after valve replacement, collecting information on how well their heart is functioning and their quality of life. Alongside this, we will comprehensively screen extracellular vesicles present in their blood to identify predictors of poor prognosis. Together this information will enable us to identify new markers associated with patient outcome, an important step towards the development of a much needed tool for AS disease management that can be used to identify the highest risk individuals for closer monitoring and timely intervention, improving patient outcomes.

The optimal iPSC-derived progeny for cardiac repair remains unknown. To date, most studies have focused on generating fully differentiated iPSC-derived cardiomyocytes (iPSC-CMs). While this approach shows promise, it is limited by the delivery of only a single replacement cell type to the injured heart. Moreover, iPSC-CMs often retain an immature phenotype, and their poor integration with host myocardium can lead to arrhythmias. In contrast, endogenous cardiac progenitor cells (eCPCs) have been widely reported to possess reparative properties. Thus, generating cardiac progenitor cells from iPSCs (iPSC-CPCs) offers an alternative, renewable source of precursors in settings where isolation of resident CPCs is not feasible. This study will directly compare human c-kit⁺ eCPCs and iPSC-CPCs isolated from the same patients, providing critical insights into their biology and therapeutic potential.