Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review

S C Glättli; F A Elzinga; W van der Bijl; H G D Leuvenink; J R Prins; H van Goor; S J Gordijn; P Olinga; D J Touw; P Mian

doi:10.1016/j.placenta.2024.03.007

Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review

Placenta. 2024 Mar 23:S0143-4004(24)00074-2. doi: 10.1016/j.placenta.2024.03.007. Online ahead of print.

Authors

S C Glättli¹, F A Elzinga¹, W van der Bijl¹, H G D Leuvenink², J R Prins³, H van Goor⁴, S J Gordijn³, P Olinga⁵, D J Touw⁶, P Mian⁷

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
² Department of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
³ Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
⁴ Department of Pathology and Medical Biology, Pathology Section, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
⁵ Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deunsinglaan 1, 9713 AV, Groningen, the Netherlands.
⁶ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deunsinglaan 1, 9713 AV, Groningen, the Netherlands.
⁷ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands. Electronic address: p.mian@umcg.nl.

PMID: 38570213
DOI: 10.1016/j.placenta.2024.03.007

Abstract

The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of ex vivo placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of preparation, control, drug, and experimental reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an ex vivo human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these ex vivo placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.

Keywords: Drug transfer; Ex vivo perfusion; Fetal exposure; Placental perfusion; Standardization.