Placental perfusion an overview of the literature

Omarini, D.; Pistotti, Vanna; Bonati, Maurizio

doi:10.1016/1056-8719(92)90048-6

Cited by 21 publications

(6 citation statements)

References 10 publications

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“…Dual perfusion of a single placental lobule ex vivo is the only experimental model to study human placental transfer of substances in organized placental tissue and theoretically may be able to more reliably predict fetal exposure compared to other experimental methods ( Table 1 ). Although tedious, the placental perfusion model has proven useful in studying both endogenous and exogenous substrates, such as amino acids, hormones, electrolytes, viruses, therapeutics, and illicit drugs 3 , 4 , 5 , 6 . This model allows simultaneous investigation of many properties that can influence placental drug transfer, such as physiochemical properties (size, the negative logarithm of the acid dissociation constant (pK a ), and lipophilicity) and pharmacokinetic factors (active transport, placental binding, and metabolism).…”

Section: Advantages and Disadvantages Of Different Methods Used To Dementioning

confidence: 99%

“…Since data from only one time point are available from these studies, the best measure for comparing in vivo data with those from perfusion studies was the F:M drug concentration ratio. A systematic search for papers that evaluated placental transfer of therapeutic drugs was performed by searching Medline, EMBASE, and EMBASE Classic from inception to 31 August 2010, using the search strategy “placenta AND perfusion” and limiting the search to human studies 4 . Perfusion studies were included if they (i) were published in English, (ii) investigated a therapeutic drug, (iii) completed dual perfusion of a term human placenta, (iv) involved placing a compound into the maternal circulation and measuring its appearance in the fetal circulation, and (v) the F:M ratio at the end of the experiment or during steady state could be extracted.…”

Section: Methodsmentioning

confidence: 99%

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The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Hutson

Garcia‐Bournissen

Davis

et al. 2011

Clin Pharmacol Ther

167

118

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Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.

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Section: Advantages and Disadvantages Of Different Methods Used To Dementioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

Hutson

Garcia‐Bournissen

Davis

et al. 2011

Clin Pharmacol Ther

167

118

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“…Furthermore, static culture conditions in these models do not reconstitute the dynamic flow environment of the placenta in vivo that has been shown to influence cellular phenotypes in the placental barrier 12 . As an alternative approach, researchers utilize ex vivo models involving controlled perfusion of the whole human placenta 13 . Although this technique has gained widespread acceptance in placental transport studies, significant challenges remain due to the requirement for human specimens, the limited amount of time that tissue remains viable, and the inconsistent results produced by these models 14 .…”

Section: Introductionmentioning

confidence: 99%

“…12 As an alternative approach, researchers utilize ex vivo models involving controlled perfusion of the whole human placenta. 13 Although this technique has gained widespread acceptance in placental transport studies, significant challenges remain due to the requirement for human specimens, the limited amount of time that tissue remains viable, and the inconsistent results produced by these models. 14 The whole organ strategy also makes highresolution analysis at the cellular and tissue levels difficult, which is often required for a mechanistic understanding of placental transport.…”

Section: Introductionmentioning

confidence: 99%

A microphysiological model of the human placental barrier

et al. 2016

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During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers – the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus. Here we present a microengineered device that provides a novel platform to mimic the structural and functional complexity of this specialized tissue in vitro. Our model is created in a multilayered microfluidic system that enables co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement to replicate the characteristic architecture of the human placental barrier. We have engineered this co-culture model to induce progressive fusion of trophoblast cells and to form a syncytialized epithelium that resembles the syncytiotrophoblast in vivo. Our system also allows the cultured trophoblasts to form dense microvilli under dynamic flow conditions and to reconstitute expression and physiological localization of membrane transport proteins, such as glucose transporters (GLUTs), critical to the barrier function of the placenta. To provide a proof-of-principle for using this microdevice to recapitulate native function of the placental barrier, we demonstrated physiological transport of glucose across the microengineered maternal-fetal interface. Importantly, the rate of maternal-to-fetal glucose transfer in this system closely approximated that measured in ex vivo perfused human placentas. Our “placenta-on-a-chip” platform represents an important advance in the development of new technologies to model and study the physiological complexity of the human placenta for a wide variety of applications.

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“…Clinical observations indicate that it may be active [5, 6] and selective [7]. The dual in vitro perfusion of an isolated placental lobule has been used for more than a decade as a model to study immunoglobulin transport [8, 9]. Using this model, peroxidase-conjugated IgG was shown to cross from the maternal to the fetal compartment within 10–60 min [10].…”

Section: Introductionmentioning

confidence: 99%

Receptor-Mediated Maternofetal Transfer of ImmunoglobulinsInhibition of Transport of Anti-HIV-1 Immunoglobulin by Generic Immunoglobulins in the in vitro Perfused Placenta

Landor¹,

Rubinstein²,

Kim³

et al. 1998

Int Arch Allergy Immunol

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Objectives: The passage of immunoglobulin G (IgG) across the placenta is thought to involve Fc’ receptors on the syncytiotrophoblast. To confirm the receptor dependency of this process we have studied the changes in the tissue content and transfer kinetics of immunoglobulins and hyperimmune serum to HIV (HIVIG) during in vitro dual placental perfusion. Methods: Isolated lobules of term placentae from normal pregnancies were perfused in a model of maternal and fetal circulation. The perfused tissue was compared to fresh tissue samples from the same placenta for the content of IgG, IgG subclasses, IgM, cytokeratin, human placental lactogen and SP1 antigen by immunohistochemistry and by protein elution. Results: The immunoglobulin staining faded by an average of 40% during the 1st hour of perfusion. In contrast, staining for cytokeratin, human placental lactogen and SP1 remained unchanged. During a 4-hour recycling of endogenous immunoglobulins in the maternal circulation, IgG and HIVIG crossed to the fetal side in a steady rate. The transport of HIVIG could be inhibited by preperfusion with an intravenous gammaglobulin preparation (IVIG). Discussion: The transfer of IgG across the placenta occurs in a steady state rate consistent with a receptor-mediated mechanism. Furthermore, inhibition of HIVIG maternofetal transfer by IVIG further establishes the receptor-mediated transfer of immunoglobulins through the placenta.

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Placental perfusion an overview of the literature

Cited by 21 publications

References 10 publications

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

A microphysiological model of the human placental barrier

Receptor-Mediated Maternofetal Transfer of ImmunoglobulinsInhibition of Transport of Anti-HIV-1 Immunoglobulin by Generic Immunoglobulins in the in vitro Perfused Placenta

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