Preliminary interlaboratory comparison of the ex vivo dual human placental perfusion system

Myllynen, Päivi; Mathiesen, Line; Weimer, Marc; Annola, Kirsi; Immonen, Elina; Karttunen, Vesa; Kummu, Maria; Mørck, Thit Juul; Nielsen, Jeanette K.; Knudsen, Lisbeth E.; Vähäkangas, Kirsi

doi:10.1016/j.reprotox.2010.04.006

Cited by 42 publications

(28 citation statements)

References 26 publications

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“…Control experiments without cells or in the absence of placental tissue were carried out in order to account for these differences as well as any loss of fluorescence over time. No significant differences in transport of substances were observed upon consideration of placental source, as reported in the comparison of placentas obtained from caesarean section versus vaginal deliveries in the inter-laboratory investigations of Myllynen et al (2010), which included placentas perfused in our laboratory. Some of the loss of fluorescence observed in the stability studies could be due to fluorescence quenching in particle agglomerates or the sedimentation of such agglomerates out of suspension.…”

Section: Discussionmentioning

confidence: 62%

Kinetics of silica nanoparticles in the human placenta

et al. 2013

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The potential medical applications of nanoparticles warrant their investigation in terms of biodistribution and safety during pregnancy. The transport of silica nanoparticles (NPs) across the placenta was investigated using two models of maternal-fetal transfer in human placenta, namely, the BeWo b30 choriocarcinoma cell line and the ex vivo perfused human placenta. Nanotoxicity in BeWo cells was examined by the MTT assay and demonstrated decreased cell viability at concentrations greater than 100 μg/mL. In the placental perfusion experiments, antipyrine crossed the placenta rapidly, with a fetal/maternal ratio of 0.97 ± 0.10 after 2 hours. In contrast, the percentage of silica NPs reaching the fetal perfusate after 6 hours was limited to 4.2 ± 4.9% and 4.6 ± 2.4% for 25-nm and 50-nm NPs, respectively. The transport of silica NPs across the BeWo cells was also limited, with an apparent permeability of only 1.54 × 10−6 ± 1.56 × 10−6 cm/sec. Using confocal microscopy, there was visual confirmation of particle accumulation in both BeWo cells and in perfused placental tissue. Despite the low transfer of silica NPs to the fetal compartment, questions regarding biocompatibility could limit the application of unmodified silica NPs in biomedical imaging or therapy.

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Section: Discussionmentioning

confidence: 62%

Kinetics of silica nanoparticles in the human placenta

et al. 2013

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“…The protocol has evolved over time and can vary between different research groups especially concerning the flow rate, composition of perfusion medium, form of oxygenation and heating 26,27 . Especially the flow rate can influence the time at which transplacental transfer occurs.…”

Section: Discussionmentioning

confidence: 99%

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

Grafmüller

Manser

Krug

et al. 2013

JoVE

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Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1 . Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3 , can serve as an excellent model to study the transfer of xenobiotics or particles.Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results.The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. Video LinkThe video component of this article can be found at

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“…BeWo cell transfer results may suffice if they are found to be consistent with the expected based on substance properties [20], but if more complete information is preferred, further investigation with the more complex ex vivo placental perfusion model is recommended [23]. The purpose of the study can also affect the choice of the model, as the placental perfusion model reflects interindividual differences in transport regarding receptors and metabolism, whereas the BeWo cell line is derived from one individual and gives a more homogenous result.…”

Section: Comparison Of the Placental Perfusion Model And The Bewo Celmentioning

confidence: 99%

“…(EtOH). Three placental perfusion laboratories were involved in the perfusions, and commonly agreed protocols generated within the European research programmes of ReProTect (Development of a novel approach in hazard and risk assessment of reproductive toxicity by a combination and application of in vitro, tissue and sensor technologies) and NewGeneris were used [23]. Perfusion transport data of investigated chemicals were compared and categorized according to their ability to pass the placental barrier.…”

Section: Substancementioning

confidence: 99%

Modelling of Human Transplacental Transport as Performed in Copenhagen, Denmark

Mathiesen

Mørck

Zuri

et al. 2014

Basic Clin Pharma Tox

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Placenta perfusion models are very effective when studying the placental mechanisms in order to extrapolate to reallife situations. The models are most often used to investigate the transport of substances between mother and foetus, including the potential metabolism of these. We have studied the relationships between maternal and foetal exposures to various compounds including pollutants such as polychlorinated biphenyls, polybrominated flame retardants, nanoparticles as well as recombinant human antibodies. The compounds have been studied in the human placenta perfusion model and to some extent in vitro with an established human monolayer trophoblast cell culture model. Results from our studies distinguish placental transport of substances by physicochemical properties, adsorption to placental tissue, binding to transport and receptor proteins and metabolism. We have collected data from different classes of chemicals and nanoparticles for comparisons across chemical structures as well as different test systems. Our test systems are based on human material to bypass the extrapolation from animal data. By combining data from our two test systems, we are able to rank and compare the transport of different classes of substances according to their transport ability. Ultimately, human data including measurements in cord blood contribute to the study of placental transport.With our work, we contribute to the paradigm shift in toxicology research from the use of animal studies towards alternative models with high relevance to human beings. Modes of actions, exposures and analysis can be studied with modelling, new omics technologies and in silico testing, preferably including study material of human origin [1,2]. Replacement of animal use in this area calls for human mechanistic and human toxicity pathway analysis bridged with exposure information as currently developed in the USA in the report Toxicity Testing in the 21st Century: A Vision and a Strategy [3], which also includes transport studies across cellular barriers such as the placenta.Risks from prenatal exposure to environmental toxicants are highly dependent on placental transport of substances from the maternal circulation to the foetal circulation. The presence of a substance in human cord blood is the ultimate demonstration of transport during pregnancy. Placental transport kinetics can be investigated by using the human dually perfused recirculating placental perfusion model and the BeWo cell transfer model.In the placental perfusion model, a human term placenta is obtained directly after birth and a single cotyledon is reperfused in the laboratory set-up. Foetal and maternal circulations are re-established by a pump system, and the transport of a chosen test substance can be investigated. This perfusion model is a simplified model of placental transport, and it does not take all the physiological and biochemical variables in the mother and foetus into account. The model can only represent transport in the late third trimester. However, the ass...

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Preliminary interlaboratory comparison of the ex vivo dual human placental perfusion system

Cited by 42 publications

References 26 publications

Kinetics of silica nanoparticles in the human placenta

Kinetics of silica nanoparticles in the human placenta

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

Modelling of Human Transplacental Transport as Performed in Copenhagen, Denmark

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