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The Effect of the Placental Microenvironment on Drug Delivery for Treatment of Preeclampsia

Katherine M. Nelson

出版	ProQuest Dissertations & Theses, 2023
ISBN	9798380376518
URL	http://books.google.com.hk/books?id=6GBe0AEACAAJ&hl=&source=gbs_api

註釋

We then wanted to understand how the microphysiological alterations seen in PE directly impacted the ability of trophoblasts to uptake and translate LNP-delivered mRNA. We cultured two types of trophoblast cell lines on substrates of different stiffnesses, ranging from healthy to preeclamptic, with different extracellular matrix (ECM) proteins known to be dysregulated during PE. We found that both substrate stiffness and composition altered the uptake and translation of mRNA in BeWo b30 cells. In addition, the differentiation status of the cells to a healthy, fused state increased LNP transfection efficiency. However, there was no effect of substrate stiffness when HTR8 cells were transfected with LNPs. These data indicate that the physical alteration of a preeclamptic placenta must be considered when developing novel therapies to treat the disease, as the cells themselves may become dysregulated and respond to the therapeutic differently than cells in a healthy placenta.