Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kupper, N.
Extracellular vesicles from advanced placental explant flow culture and their role in preeclampsia
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Gauster Martin
- Huppertz Berthold
- Mayer-Pickel Karoline Ilse
- Altmetrics:
- Abstract:
- A healthy human placenta represents a highly functional organ, enabling the development of the growing fetus. It acts as fetal-maternal interface embedded within a dynamic system of circulating maternal blood and blood-borne substances. A healthy pregnancy is dependent on the biochemical and morphological integrity of the placenta, including a balanced feto-maternal crosstalk. Placental malfunctions are associated with diverse pregnancy pathologies with emphasis on preeclampsia (PE). It represents a global pregnancy syndrome with increasing significance but still unknown etiology. In general, the pathophysiology of this syndrome is associated to placental dysfunction as well as to diverse maternal organ malfunctions. A growing amount of studies has already tried to elucidate the various hypotheses and scenarios associated to the diverse characteristics of preeclampsia with a mostly general consensus that placental extracellular vesicles (EVs) play a role in the development of this syndrome. In this thesis, I established a novel ex vivo flow culture system for placental explants mimicking an in-utero like dynamic situation. This cultivation mode was shown to improve tissue integrity of in vitro cultured placental tissue compared to the commonly used static method. Furthermore, this system was used to simulate the in vivo situation regarding the release of EVs from the placenta into the maternal circulation. Analysis of isolated EVs derived from cultivated normotensive (NP) and PE placental explants supported the notion of increased EV release from PE placenta samples. Furthermore, uptake analysis revealed that EVs are predominantly internalized into endothelial cells after 4h of exposure under constant flow conditions. No significant differences in the uptake pattern between PE-EVs and NP-EVs were found, regarding the localization of EVs. Furthermore, it was shown that NP-EVs and PE-EVS derived from flow cultured placental explants were associated with a release of Flt1/VEGFR1 but not with PlGF. In summary, this thesis contributes to the understanding of the role of EVs in pregnancy. It further provides new insights into a gentle and still simple technique for ex vivo placental explant culture thus, emphasizing the importance of executable dynamic approaches for studies on the biological functions of the placenta.