Heart valve disease leads to permanent damage to the valve leaflets and can arise developmentally, through infection, or through age-related degeneration. Largely due to the lack of knowledge surrounding the etiopathogenesis of heart valve disease, there are currently no pharmacological treatments that can halt or reverse heart valve damage. Our goal is to utilise stem cell-derived heart valve cells to develop a new valve prosthesis for surgical treatment of disease that accurately mimics the characteristics of native heart valves. Moreover, through disease modelling, we hope to uncover the underlying causes and mechanisms of heart valve disease.
Impact
With the increasing burden of heart valve disease across Australian demographics and worldwide, there is a fundamental requirement for this knowledge gap to be addressed. By investigating an alternative cellular therapy and exploring the pathogenesis and biological mechanisms of inflammatory valve diseases, we hope to interfere with disease progression, develop preventative measures and interventions, and overall improve the clinical treatment and outcomes of heart valve disease.
reNEW research
Our team has developed a human pluripotent stem cell-derived heart valve model that leverages the infinite nature of stem cells. Utilising this protocol, we are able to generate three-dimensional valve engineered tissues of both micro- and macro scale for disease modelling and therapeutic applications. We have performed proof-of-concept experiments to showcase the future application of the macro tissues as a valve prosthesis and have demonstrated the feasibility and applicability of the micro tissues to model heart valve diseases such as rheumatic heart disease and calcific aortic valve disease.
Image description
This image shows a pluripotent stem cell-derived heart valve engineered macro tissue. These tissues can measure between 1cm and 6cm in diameter with a cell input of 0.5-50e6 cells. This enables us to observe the cell morphology and fibre organisation in response to external stimuli, such as stretch and flow, to best mimic the native heart valve.
Credits
Jessica Durrant-Whyte, Research Assistant Porrello Lab, reNEW Melbourne.
