"Studies on the induction and delay of senescence in the human placenta explants model (keyword: therapy-induced senescence, TIS)"
cand. Dr. med. Emily Könnecke
supervisor Dr. rer. nat. Astrid Schmidt
funded by IZKF 2023
The placenta laboratory offers the special opportunity to cultivate placentas in vitro directly after birth and thus to study a human model system. For this purpose, explants are cultivated over a period of up to two weeks under various conditions. It is known that the syncytiotrophoblast (STB) initially degenerates in the first few days and can then be functionally reconstituted by the cytotrophoblast (CTB) (1,2). Chuprin, 2013, showed that the STB, in contrast to the CTB, shows both phenotype and markers for senescence. The degeneration and regeneration of the STB from the CTB in culture is therefore subject to senescence processes, which should be investigated with the focus on the extent to which the senescence of the placental villi can be inhibited or induced. For this purpose, explants will be cultivated under different conditions with regard to induction and inhibition and the tissue will be examined for senescence markers. Immunohistochemical staining, vitality and hormone analyses as well as electron microscopic examinations of the transformation of mitochondria as markers for senescence are planned. PCR analyses for senescence markers in tissue and in extracellular vesicles from culture supernatants are also planned.
- Simán CM, Sibley CP, Jones CJP, Turner MA, Greenwood SL. 2001. The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 280(4):R1116-R1122.
- Schulz (2019) Optimierung der 14-tägigen Kultivierung von humanen Plazenta Explantaten mit anschließendem Toxizitäts-Assay (Masterarbeit, Placenta-Labor)
- Chuprin A, Gal H, Biron-Shental T, Biran A, Amiel A, Rozenblatt S, Krizhanovsky V. 2013. Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. Genes & Development, 27(21):2356-2366.