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The Heart-Brain Axis : Modelling the heart-brain axis using innovative organ-on-chip technology

Sterckel, S.A. (2023) The Heart-Brain Axis : Modelling the heart-brain axis using innovative organ-on-chip technology.

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Abstract:The heart-brain axis represents a complex interplay between the cardiovascular and nervous systems, influencing physiological responses crucial for maintaining homeostasis. An illustrative example of this intricate connection is evident in the pathology of heart failure, where aberrant signaling between the heart and brain exacerbates the disease progression[1]. This thesis addresses the critical need to model the heart-brain axis for disease understanding, focusing on its impact on heartbeat regulation. The primary goal is to develop an innovative model utilizing human pluripotent stem cells (hPSCs) on a microfluidic chip to mimic the brain's influence on cardiac function through autonomic nervous system (ANS) cell innervation. Key achievements of the project include successful differentiations of cardiac embryoid bodies (cEBs), brain organoids (BO), and vagal nerve-like cells from human embryonic stem cells (hESCs). Notably, a sympathetic nerve-like cell differentiation was introduced to counter vagal heartbeat regulation, presenting morphological distinctions. Additionally, project optimization involved testing cryopreservation of beating cEBs, various density seeding for different sized BOs, and simulating on-chip conditions. The microfluidic chip, designed for controlled co-culture of these components, achieved controlled cell localization and hydrostatic perfusion of all compartments. This design addressed handling challenges, improved live cell staining, and could accommodate four distinct cell type. This comprehensive approach contributes to advancing our understanding of the heart-brain axis, providing a foundation for disease modeling and therapeutic research. The ability to control cell localization and simulate on- chip conditions offers new opportunities for studying cardiac regulation influenced by neural connections. In the future, this research paves the way for in-depth investigations into disease-specific mechanisms, personalized medicine approaches, and the development of innovative therapies targeting the heart-brain axis.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:42 biology, 50 technical science in general
Programme:Biomedical Engineering MSc (66226)
Link to this item:https://purl.utwente.nl/essays/98004
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