Graduate Student Seminar Series – Melody Li

Graduate Student Seminar Series
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Location: WB116
Presentation Title: Vascularized Heart-on-a-chip for Recapitulating Physiological Complexity
Abstract:
*Rationale: Modeling physiological cardiac tissue and its disease responses accurately has been a crucial task for researchers to streamline therapeutics development and enhance drug screening efficiency. This is however difficult due to the complex composition and interaction of the heart, including the intricate vessel network plays an important role in modulating cardiac function. There exists a clear gap in developing a three-dimensional physiological platform that mimics cell interactions to capture accurate cardiac responses. The focus of my thesis work is to develop an in vitro engineered heart-on-a-chip platform with perfusable vasculature, which can be used for higher-fidelity therapeutic screening of cardiovascular diseases;
*Methods: We designed a thermoplastic-based platform, where hPSC-derived CM self-organized into 3D between flexible rods near a central microwell. After cardiac construct formation, ECs and stromal cells were introduced to self-organize into the microvascular network with gravity-driven media flow. After 3 weeks of co-culturing, contractile force and vessel properties were assessed to investigate the effect of bi-directional interactions on cardiac tissue and microvasculature. The platform can be used to test anti-fibrotic drugs like lisinopril and observe changes in tissue stiffness and microvasculature functionality in a fibrosis model.
*Results: For preliminary results, a perfusable microvasculature formed by ECs and stromal cells was established and the selective permeability of the vasculature was tested by the fluorescent dextran. Cardiac tissue is expected to exhibit maturation hallmarks with the presence of perfusable vasculature.
*Conclusion/Significance: The vascularized heart-on-a-chip model will capture key hallmarks of cardiac development and microvascular dysfunction, promoting advanced tissue maturity and stable function for up to a month. The study will therefore provide a valuable tool for high-fidelity therapeutic screening, aiding in the management of cardiovascular pathology and the development of new functional myocardium.
Supervisor Name: Sara Vasconcelos
Year of Study: 3
Program of Study: PhD
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