Placenta-on-a-Chip as an In Vitro Approach to Evaluate the Physiological and Structural Characteristics of the Human Placental Barrier upon Drug Exposure: A Systematic Review

Abstract

Quantification of fetal drug exposure remains challenging since sampling from the placenta or fetus during pregnancy is too invasive. Currently existing in vivo (e.g., cord blood sampling) and ex vivo (e.g., placenta perfusion) models have inherent limitations. A placenta-on-a-chip model is a promising alternative. A systematic search was performed in PubMed on 2 February 2023, and Embase on 14 March 2023. Studies were included where placenta-on-a-chip was used to investigate placental physiology, placenta in different obstetric conditions, and/or fetal exposure to maternally administered drugs. Seventeen articles were included that used comparable approaches but different microfluidic devices and/or different cultured maternal and fetal cell lines. Of these studies, four quantified glucose transfer, four studies evaluated drug transport, three studies investigated nanoparticles, one study analyzed bacterial infection and five studies investigated preeclampsia. It was demonstrated that placenta-on-a-chip has the capacity to recapitulate the key characteristics of the human placental barrier. We aimed to identify knowledge gaps and provide the first steps towards an overview of current protocols for developing a placenta-on-a-chip, that facilitates comparison of results from different studies. Although models differ, they offer a promising approach for in vitro human placental and fetal drug studies under healthy and pathological conditions.

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies

“…19–21 OOCs can overcome several limitations of conventional in vitro 2D cultures of the placenta by providing a structural layout to accommodate multiple cell types in a single platform while allowing intercellular interaction and interchange of secreted factors, extracellular vesicles, and even cellular migration through the chamber-to-chamber junctions. The latest advancements in the placenta OOC model have been recently summarized by Elzinga et al 22 The most widely described models include two-cell chips, which have trophoblasts and endothelial cell compartments. 23–32 Single-cell chips have also been developed, in which only trophoblast cells are maintained, 33,34 while a three-chamber chip has also been developed from the Menon Laboratory, which includes cytotrophoblasts, syncytiotrophoblasts, and endothelial cells.…”