Ex Vivo Dual Perfusion of the Human Placenta: Disease Simulation, Therapeutic Pharmacokinetics and Analysis of Off-Target Effects

Brownbill, Paul; Sebire, Neil J.; McGillick, Erin V.; Ellery, Stacey J.; Murthi, Padma

doi:10.1007/978-1-4939-7498-6_14

Cited by 23 publications

(24 citation statements)

References 47 publications

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“…Perfusion has advantages over cell culture, tissue slices and explant studies due to the maintenance of villous architecture and relative IVS volume density (Brownbill et al . ). Vascularised fetoplacental and IVS perfusate flows are key features of the model in which the placental tissue maintains a higher metabolic level than in other human placental models (Hauguel et al .…”

Section: Introductionmentioning

confidence: 97%

Human placental oxygenation in late gestation: experimental and theoretical approaches

Nye

Ingram

Johnstone

et al. 2018

The Journal of Physiology

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The placenta is crucial for life. It is an ephemeral but complex organ acting as the barrier interface between maternal and fetal circulations, providing exchange of gases, nutrients, hormones, waste products and immunoglobulins. Many gaps exist in our understanding of the detailed placental structure and function, particularly in relation to oxygen handling and transfer in healthy and pathological states in utero. Measurements to understand oxygen transfer in vivo in the human are limited, with no general agreement on the most appropriate methods. An invasive method for measuring partial pressure of oxygen in the intervillous space through needle electrode insertion at the time of Caesarean sections has been reported. This allows for direct measurements in vivo whilst maintaining near normal placental conditions; however, there are practical and ethical implications in using this method for determination of placental oxygenation. Furthermore, oxygen levels are likely to be highly heterogeneous within the placenta. Emerging non‐invasive techniques, such as MRI, and ex vivo research are capable of enhancing and improving current imaging methodology for placental villous structure and increase the precision of oxygen measurement within placental compartments. These techniques, in combination with mathematical modelling, have stimulated novel cross‐disciplinary approaches that could advance our understanding of placental oxygenation and its metabolism in normal and pathological pregnancies, improving clinical treatment options and ultimately outcomes for the patient.

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Section: Introductionmentioning

confidence: 97%

Human placental oxygenation in late gestation: experimental and theoretical approaches

Nye

Ingram

Johnstone

et al. 2018

The Journal of Physiology

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“…Although in vitro DNA hybridization kinetics based on some sequences have led to a set of mature theories (Dirks and Pierce, 2003, 2004; Dirks et al, 2004, 2007; SantaLucia and Hicks, 2004; Zhang and Winfree, 2009; Zadeh et al, 2011; Zhang et al, 2012, 2018a; Wolfe and Pierce, 2015; Wolfe et al, 2017), a basic theory for quantifying miRNA in vivo is still lacking, which is restricted by technologies in other related fields, such as fluorescence reconstruction (Ntziachristos and Weissleder, 2001; Dirks and Pierce, 2003; Cong and Wang, 2005; Lasser et al, 2008; Zhang et al, 2015; Shibata et al, 2017), pharmacokinetics (Brownbill et al, 2018; Caro et al, 2018; Sharma et al, 2018), and others. To quantify miRNA in vivo , the in vitro reaction kinetics of SQ, FP, and the target miRNA must be accurately modeled mathematically.…”

Section: Resultsmentioning

confidence: 99%

An Artificial Intelligent Signal Amplification System for in vivo Detection of miRNA

Chen

Yang

et al. 2019

Front. Bioeng. Biotechnol.

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MicroRNAs (miRNA) have been identified as oncogenic drivers and tumor suppressors in every major cancer type. In this work, we design an artificial intelligent signal amplification (AISA) system including double-stranded SQ (S, signal strand; Q, quencher strand) and FP (F, fuel strand; P, protect strand) according to thermodynamics principle for sensitive detection of miRNA in vitro and in vivo. In this AISA system for miRNA detection, strand S carries a quenched imaging marker inside the SQ. Target miRNA is constantly replaced by a reaction intermediate and circulatively participates in the reaction, similar to enzyme. Therefore, abundant fluorescent substances from S and SP are dissociated from excessive SQ for in vitro and in vivo visualization. The versatility and feasibility for disease diagnosis using this system were demonstrated by constructing two types of AISA system to detect Hsa-miR-484 and Hsa-miR-100, respectively. The minimum target concentration detected by the system in vitro (10 min after mixing) was 1/10th that of the control group. The precancerous lesions of liver cancer were diagnosed, and the detection accuracy were larger than 94% both in terms of location and concentration. The ability to establish this design framework for AISA system with high specificity provides a new way to monitor tumor progression and to assess therapeutic responses.

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“…A number of publications have addressed placental EVs and their potential role in pregnancy and its complications . Several ex vivo (eg, placental perfusion) and in vivo systems have been used as a source of EVs. Placental perfusion is a useful method for obtaining large numbers of EVs directly from the placenta; however, this technique is suitable only for a short period of time (2‐6 hours) after delivery .…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

Fitzgerald

Gomez‐Lopez

Erez

et al. 2018

American J Rep Immunol

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A system of ex vivo placental villous and amnion tissues can be used as an adequate model to study placenta metabolic activity in normal and complicated pregnancies, in particular to characterize EVs by their surface markers and by encapsulated proteins. Establishment and benchmarking the placenta ex vivo system may provide new insight in the functional status of this organ in various placental disorders, particularly regarding the release of EVs and cytokines. Such EVs may have a prognostic value for pregnancy complications.

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Ex Vivo Dual Perfusion of the Human Placenta: Disease Simulation, Therapeutic Pharmacokinetics and Analysis of Off-Target Effects

Cited by 23 publications

References 47 publications

Human placental oxygenation in late gestation: experimental and theoretical approaches

Human placental oxygenation in late gestation: experimental and theoretical approaches

An Artificial Intelligent Signal Amplification System for in vivo Detection of miRNA

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

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