TY - JOUR

T1 - Ex vivo dual perfusion of an isolated human placenta cotyledon

T2 - Towards protocol standardization and improved inter-centre comparability

AU - Schneider, Henning

AU - Albrecht, Christiane

AU - Ahmed, Mahmoud S.

AU - Broekhuizen, Michelle

AU - Aengenheister, Leonie

AU - Buerki-Thurnherr, Tina

AU - Danserf, A. H. Jan

AU - Gil, Sophie

AU - Hansson, Stefan R.

AU - Greupink, Rick

AU - Lewis, Rohan M.

AU - Markert, Udo R.

AU - Mathiesen, Line

AU - Powles-Glover, Nicola

AU - Wadsack, Christian

AU - Brownbill, Paul

PY - 2022

Y1 - 2022

N2 - Since the full development of the ex vivo dual perfusion model of the human placenta cotyledon, the technique has provided essential insight into how nutrients, lipids, gases, immunoglobulins, endocrine agents, pharma-ceuticals, chemicals, nanoparticles, micro-organisms and parasites might traverse the maternofetal barrier. Additionally, the model has been instrumental in gaining a better understanding of the regulation of vascular tone, endocrinology and metabolism within this organ. The human placenta is unique amongst species in its anatomy and transfer modalities. This orthologous diversity therefore requires an appropriate consideration of placental transfer rates of compounds, particles and micro-organisms specific to humans. Different research centres have adapted this model with a wide variation in perfusion parameters, including in the establishment of perfusion, perfusate composition, gassing regime, cannulation method, flow rates, perfused tissue mass, and also in the application of quality control measures. The requirement to harmonise and stan-dardise perfusion practice between centres is largely driven by the need to obtain consistency in our under -standing of placental function, but also in the qualification of the model for acceptance by regulatory agencies in drug and toxicology testing. A pilot study is proposed, aiming to describe how existing inter-centre variation in perfusion methodology affects placental metabolism, protein synthesis, oxygen consumption, the materno-fetal transfer of key molecular markers, and placental structure.

AB - Since the full development of the ex vivo dual perfusion model of the human placenta cotyledon, the technique has provided essential insight into how nutrients, lipids, gases, immunoglobulins, endocrine agents, pharma-ceuticals, chemicals, nanoparticles, micro-organisms and parasites might traverse the maternofetal barrier. Additionally, the model has been instrumental in gaining a better understanding of the regulation of vascular tone, endocrinology and metabolism within this organ. The human placenta is unique amongst species in its anatomy and transfer modalities. This orthologous diversity therefore requires an appropriate consideration of placental transfer rates of compounds, particles and micro-organisms specific to humans. Different research centres have adapted this model with a wide variation in perfusion parameters, including in the establishment of perfusion, perfusate composition, gassing regime, cannulation method, flow rates, perfused tissue mass, and also in the application of quality control measures. The requirement to harmonise and stan-dardise perfusion practice between centres is largely driven by the need to obtain consistency in our under -standing of placental function, but also in the qualification of the model for acceptance by regulatory agencies in drug and toxicology testing. A pilot study is proposed, aiming to describe how existing inter-centre variation in perfusion methodology affects placental metabolism, protein synthesis, oxygen consumption, the materno-fetal transfer of key molecular markers, and placental structure.

KW - Placenta

KW - Perfusion

KW - Transfer

KW - Function

KW - Regulatory

KW - Standardisation

KW - IN-VITRO

KW - OXYGEN-CONSUMPTION

KW - BLOOD-FLOW

KW - RELEASE

KW - PERMEABILITY

KW - DETERMINANT

KW - TRANSPORT

KW - ALBUMIN

KW - STRESS

KW - GASES

U2 - 10.1016/j.placenta.2022.05.003

DO - 10.1016/j.placenta.2022.05.003

M3 - Journal article

C2 - 35785693

VL - 126

SP - 83

EP - 89

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -