Engineering Innate Immunology in a Humanised, Functional, In Vitro Model of Healthy Myocardium
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2024Author:
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2026-04-12Citation:
Suku, Meenakshi, Engineering Innate Immunology in a Humanised, Functional, In Vitro Model of Healthy Myocardium, Trinity College Dublin, School of Engineering, Mechanical & Manuf. Eng, 2024Download Item:
Meena Suku PhD Thesis Final.pdf (PhD Thesis) 47.81Mb
Abstract:
Cardiovascular disease stands as the leading cause of death globally, claiming approximately
19.05 million lives in 2020. On the contrary, the development of cardiovascular drugs is
experiencing a decline, largely due to the complexities involved in understanding the
pathophysiology of various heart diseases and assessing the effects of drugs on healthy
human hearts. The development of induced pluripotent stem cell (iPSC) technology and the
availability of cardiac cell types in vitro, has resulted in a surge in efforts to fabricate human
cardiac models for disease modelling and drug discovery applications. Although numerous
attempts evidence successful fabrication of 3 dimensional (3D) engineered heart tissues, the
innate immune cell population of the myocardium ¿ particularly cardiac macrophages, are
almost always overlooked. With increasing appreciation of the interactions between
cardiomyocytes and macrophages in the myocardium, in this work, a 3D engineered heart
tissue model of the myocardium was fabricated, with iPSC-derived cardiomyocytes (iCMs),
macrophages (iMacs) and cardiac fibroblasts (iCFs), all from the same iPSC parent line. After
characterising iCMs, iCFs and iMacs in depth, the conditioning of iMacs to align to a cardiac
resident macrophage-like phenotype in the presence of iCMs in monolayer culture is
explored. Subsequently, the effect of electrical stimulation on iCMs, iMacs and iCM/iMac
co-cultures, is investigated. The 2D characterisation is translated into an engineered heart
tissue model, wherein, improvement in tissue characteristics in the presence of iMacs is
demonstrated. Finally, the addition of myofibroblasts (activated iCFs) into the tissues is
explored, as a preliminary platform for modelling cardiac tissue fibrosis.
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Author: Suku, Meenakshi
Advisor:
Monaghan, MichaelPublisher:
Trinity College Dublin. School of Engineering. Discipline of Mechanical & Manuf. EngType of material:
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