Abstract
The human placenta plays a crucial role as the interface between mother and fetus. It represents a unique tissue that undergoes morphological as well as functional changes on the cellular and tissue level throughout pregnancy. To better understand how the placenta works, a variety of techniques has been developed to re-create this complex physiological barrier in vitro. However, due to the low availability of freshly isolated primary cells, choriocarcinoma cell lines remain the usual suspects as in vitro models for placental research. Here, we present a comparative study on the functional aspects of the choriocarcinoma cell lines BeWo, JAR and Jeg-3, as well as the first trimester trophoblast cell line ACH-3P as placental in vitro barrier models for endocrine and transport studies. Functional assays including tight junction immunostaining, sodium fluorescein retardation, trans epithelial resistance, glucose transport, hormone secretion as well as size-dependent polystyrene nanoparticle transport were performed using the four cell types to evaluate key functional parameters of each cell line to act a relevant in vitro placental barrier model.
Highlights
The human placenta plays a crucial role in the development and health of the fetus as the interface between mother and fetus by regulating nutrient and oxygen transport from the mother to the fetus as well as releasing fetal waste products into the maternal circulation
Human placental villi of the villous trees are covered by a highly specialized two-layered epithelium-like layer, the villous trophoblast
Proliferation is restricted to a small subset of progenitor cells, which divide asymmetrically and undergo differentiation resulting in fusion with the overlying syncytium[13, 14]
Summary
The human placenta plays a crucial role in the development and health of the fetus as the interface between mother and fetus by regulating nutrient and oxygen transport from the mother to the fetus as well as releasing fetal waste products into the maternal circulation. The ex vivo human placental perfusion model, which was originally developed by Panigel and co-workers in 196226, 27, provides a controlled system for studying trans-placental transport and is commonly used for pharmacokinetic studies This model allows the investigation of molecule and material transfer on a whole-organ scale with organized tissue architecture[28,29,30,31], it exhibits poor reproducibility, low throughput capabilities and no standardization at all. The placenta is an organ that undergoes severe morphological changes during gestation that alter materno-fetal transport mechanisms severely[33] To overcome these limitations, a lot of research effort so far has focused on how to recreate physiologically meaningful placental models using in vitro cell cultures. To reduce the use of or even replace animal models, today’s in vitro cell cultures need to improve with respect to organ function and physiological relevance
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