{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:05:21Z","timestamp":1773011121655,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030\u2010197408"],"award-info":[{"award-number":["310030\u2010197408"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Although women often need to take medication during pregnancy, reliable human\u2010based models mimicking the maternal\u2013fetal interface and allowing predictions on drug transport across the human placenta are scarce. In this study, we developed a novel microfluidic Transwell\u2010based co\u2010culture model consisting exclusively of primary cells (trophoblasts\/endothelial cells) for assessing maternal\u2013fetal drug transfer. We aimed to (1) investigate the effects of fluidic flow on drug transfer patterns, (2) evaluate barrier integrity and different transfer processes (diffusion, active transport) across the combined trophoblast\/endothelial monolayers and (3) determine the expression and functional activity of main placental drug efflux transporters (ABCB1 and ABCG2). After applying different flow rates (50\/150\u00a0\u00b5l\/min), our system maintained cellular integrity and barrier function while enhancing syncytialization markers such as hCG. Our model effectively mimics key features of the placental microenvironment, including polarized expression and functional activity of both efflux transporters. Using fluorescent substrates and specific inhibitors (ABCB1: Rhodamine 123\/Cyclosporin A; ABCG2: Bodipy\u2010FL\u2010Prazosin\/Ko123), we confirmed that both transporters are not only expressed in the primary co\u2010cultures, but also actively restrict the passage of compounds in the mother\u2010to\u2010fetus direction. Importantly, our system also captured passive diffusion dynamics of reference compounds (antipyrine\/caffeine), with transport rates increasing under higher flow, mirroring\n in vivo<\/jats:italic>\n behaviour. While our model does not yet replicate the full complexity of the placenta, our findings provide strong evidence that dynamic flow systems can recapitulate key placental transport phenomena and offer a valuable\n in vitro<\/jats:italic>\n model to study human\u2010based transplacental transport processes.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Medication use during pregnancy is an essential aspect of obstetrical care, it remains a major concern due to potential risks to fetal and placental development.<\/jats:p>\n <\/jats:list-item>\n \n \n Current\n in vitro<\/jats:italic>\n models for assessing maternal\u2013fetal drug transfer mostly consist of immortalized cell lines and\/or lack critical components of the placental microenvironment, such as stromal cells or dynamic fluid flow.\n <\/jats:p>\n <\/jats:list-item>\n \n We developed a dynamic Transwell\u2010based co\u2010culture model , composed exclusively of primary trophoblast and endothelial cells.<\/jats:p>\n <\/jats:list-item>\n \n The model effectively mimics key features of the placental barrier properties, including polarized expression and functional activity of major placental drug efflux transporters.<\/jats:p>\n <\/jats:list-item>\n \n \n The dynamic primary cell based flow systems offer a physiologically relevant human\n in vitro<\/jats:italic>\n model to investigate and predict transplacental drug transfer.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289606","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:27:02Z","timestamp":1773005222000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A primary cell\u2010based fluidic co\u2010culture model to investigate drug transport across the human placenta"],"prefix":"10.1113","author":[{"given":"Barbara","family":"Fuenzalida","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja","family":"Koechli","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar","family":"Ontsouka","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chennakesava","family":"Cuddapah","sequence":"additional","affiliation":[{"name":"Curio Biotech Ltd. Visp Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Mueller","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine University of Bern Bern Switzerland"},{"name":"Division of Gynecology and Obstetrics Lindenhofgruppe Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bram","family":"Sengers","sequence":"additional","affiliation":[{"name":"Bioengineering Sciences Research Group, Faculty of Engineering and Physical Sciences University of Southampton Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frantisek","family":"Staud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove Charles University Hradec Kralove Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-6930","authenticated-orcid":false,"given":"Christiane","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, Faculty of Medicine University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-019-06257-2"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.54"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-19-1379-2_16"},{"issue":"2","key":"e_1_2_6_5_1","article-title":"Placental drug transport\u2010on\u2010a\u2010chip: A microengineered in vitro model of transporter\u2010mediated drug efflux in the human placental barrier","volume":"7","author":"Blundell C.","year":"2018","journal-title":"Advanced Healthcare Materials"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-01114-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/mi12080884"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12134315"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70151"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-61629-4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11121898"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202301708RR"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1499726"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00286.2008"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45279-y"},{"issue":"1","key":"e_1_2_6_16_1","first-page":"173","article-title":"Identification of placental nutrient transporters associated with intrauterine growth restriction and pre\u2010eclampsia","volume":"19","author":"Huang X.","year":"2018","journal-title":"BioMed Central Genomics [Electronic Resource]"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaw018"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.002261"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147262"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10995-017-2358-0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42522-1"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.02.029"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2009.09.033"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9871"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-19422-y"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/gch2.201800112"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2009.07.028"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04475-z"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06364-z"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166131"},{"key":"e_1_2_6_31_1","unstructured":"UMCG research. 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