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Creating physiological in\u00a0vitro models to study these processes is crucial, but technically challenging. This study introduces an efficient cell model that mimics the human placental barrier using co\u2010cultures of primary trophoblasts and primary human umbilical vein endothelial cells (HUVEC) on a Transwell<jats:sup>\u00ae<\/jats:sup>\u2010based system. Monolayer formation was examined over 7\u2009days by determining transepithelial electrical resistance (TEER), permeability of Lucifer yellow (LY) and inulin, localization of transport proteins at the trophoblast membrane (immunofluorescence), and syncytialization markers (RT\u2010qPCR\/ELISA). We analysed diffusion\u2010based (caffeine\/antipyrine) and transport\u2010based (leucine\/Rhodamine\u2010123) processes to study the transfer of physiologically relevant compounds. The latter relies on the adequate localization and function of the amino\u2010acid transporter LAT1 and the drug transporter P\u2010glycoprotein (P\u2010gp) which were studied by immunofluorescence microscopy and application of respective inhibitors (2\u2010Amino\u20102\u2010norbornanecarboxylic acid (BCH) for LAT1; cyclosporine\u2010A for P\u2010gp). The formation of functional monolayer(s) was confirmed by increasing TEER values, low LY transfer rates, minimal inulin leakage, and appropriate expression\/release of syncytialization markers. These results were supported by microscopic monitoring of monolayer formation. LAT1 was identified on the apical and basal sides of the trophoblast monolayer, while P\u2010gp was apically localized. Transport assays confirmed the inhibition of LAT1 by BCH, reducing both intracellular leucine levels and leucine transport to the basal compartment. Inhibiting P\u2010gp with cyclosporine\u2010A increased intracellular Rhodamine\u2010123 concentrations. Our in\u00a0vitro model mimics key aspects of the human placental barrier. It represents a powerful tool to study nutrient and drug transport mechanisms across the placenta, assisting in evaluating safer pregnancy therapies.<\/jats:p>","DOI":"10.1111\/jcmm.70151","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T10:39:28Z","timestamp":1729247968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modelling the maternal\u2010fetal interface: An in\u00a0vitro approach to investigate nutrient and drug transport across the human placenta"],"prefix":"10.1111","volume":"28","author":[{"given":"Barbara","family":"Fuenzalida","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Basler","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular 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