Studying Endothelial Permeability In Vitro for Diabetic Kidney Disease Research

Vika Telle

Research output: ThesisThesis fully internal (DIV)

115 Downloads (Pure)

Abstract

Endothelial cell layer is an essential component of the glomerular filtration barrier. A thorough study of endothelial layer permeability in diabetic kidney disease (DKD) contributes to the better understanding of the pathogenesis of DKD, facilitating the development of more targeted treatment strategies. Physiologically relevant in vitro test systems are crucial for obtaining reliable data. This thesis describes a step-by-step transformation of a simple, static, well-plate fluorescence-based macromolecular tracer flux assay into a microfluidic endothelium-on-a-chip for modelling DKD environment in vitro. We incorporated several elements in our in vitro system to mimic the native environment experienced by endothelial cells in the body. We modelled the DKD environment by exposing the endothelial barrier layer to several endogenous factors individually and in combinations, and were able to quantify the permeability values, as well as observe the biological effects of the tested factors on endothelial barrier integrity. As endothelial permeability is an intricately and dynamically regulated process with involvement of several structural components, we additionally studied the response of the endothelial glycocalyx - a gel-like layer covering endothelial cells - to the DKD environment.
Ultimately, we were able to test the effect of a pharmaceutical, used in the treatment of the DKD patients, in our endothelium-on-a-chip. We predict that this endothelium-on-a-chip could be applied for modelling a variety of pathophysiological conditions affecting endothelial barrier integrity, as well as for drug research targeted to improve endothelial barrier resilience.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Verpoorte, Elisabeth, Supervisor
  • Lambers Heerspink, Hiddo, Supervisor
Award date26-Mar-2024
Place of Publication[Groningen]
Publisher
DOIs
Publication statusPublished - 2024

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