Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Radauer, A.
Investigation of Senescence in Primary Fabry Disease Patient-Derived Endothelial Colony Forming Cells.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2024. pp.55.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Madreiter-Sokolowski Corina
- Tokic Silvija
- Altmetrics:
- Abstract:
- Fabry disease (FD) is an inherited lysosomal storage disorder caused by pathogenic variants in the GLA-gene, resulting in deficient or absent ⍺-galactosidase A (⍺-Gal A) activity. The lack of ⍺-Gal A activity leads to the accumulation of Gb3 in vascular endothelial cells (ECs), among others, which causes clinical manifestations of FD, such as stroke, cardiovascular disease, and renal impairment. Therefore, ECs are frequently used to study FD in vitro. These ECs stem from various sources and are often genetically modified, which makes them inadequate for association studies with clinical parameters. Endothelial colony forming cells (ECFCs) are patient-derived ECs isolated from peripheral blood and carry the whole patient’s genotype. This is particularly important when studying FD, since patients with identical genetic variants may show distinct disease phenotype. When culturing FD patient-derived ECFCs in our laboratory, they were found to have increased granularity, an enlarged and irregular shape, multinucleation, and they proliferated more slowly in comparison to ECFCs derived from healthy controls. This raised the question of whether ECFCs derived from FD patients are more prone to senescence. Senescence is defined as a mechanism by which a dividing cell, in response to a noxious or stressful stimulus, enters a stable cell-cycle arrest and generally exerts a complex secretion of factors, known as senescence-associated secretory phenotype, which affects the surrounding tissue, while remaining metabolically active and unresponsive to mitogenic and apoptotic signals.