PlaTox - Placenta Toxicology - human placental explants ...
Transcript of PlaTox - Placenta Toxicology - human placental explants ...
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This project has received funding from the European Union’s Horizon 2020 research and innovation
programme under Grant Agreement No 777554
PlaTox - Placenta Toxicology -human placental explants for
drug testing Udo R. Markert
Placenta Lab, Dept. of Obstetrics,
Jena University Hospital, GermanyEPTRI Stakeholders Roundtable
Virtual Meeting July 9th, 2020
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PlaTox - Placenta Toxicology - human placental explants for drug testing
Andreas Schober Technical University Ilmenau
Gregor Schlinghoff Technical University Ilmenau
Andre Schmidt Placenta Lab Jena
Placenta Lab
Department of ObstetricsUniversity Hospital Jena, Germany
www.placenta-labor.de
Udo R. Markert
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The human placenta
• barrier between mother and embryo / fetus
• bi-directional selective transport
• hormone production
• immunoregulation
• unique human organ freshly available
• enormous species difference
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Placenta models
• cells: isolated cells or cell lines, 2D or 3D
• whole placenta cotyledons
for placenta perfusion
• placenta explants (fragments)
aim of PlaTox
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Placenta anatomy
Cotyledon
explants
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Placenta perfusion – fetal circuit
@ Anna Schroll
• transfer• accumulationof test substances
Aim: to test
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Placenta perfusion – maternal circuit
@ Anna Schroll
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cell lines unlimited unlimited high low
placenta explants a few days high low
isolated cells a few days limited medium
one side perfusion 8 hours 1-2 / day medium
dual perfusion 8 hours 3 / week high
exposure availability reproduci- work
time bility load / n
patient-
depe
nde
nt
Göhner C, Pfarrer C, Faas M, Ernerudh J, Cline JM, Buse E, Markert UR.The placenta in toxicology. Part IV. Battery of toxicological test systems based on human placenta. Toxicol Pathol 2014;42:345-51.
Placenta models
PlaTox
> 14 days
> 96 samples
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Placenta explant culture devices
bioreactor TissGrid® MatriGrid®for superfusion
placenta villous tissue
syncytiotrophoblast
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Placenta explant estradiol production
100 µl/minsuperfusion
100 µl/minthrough flow
static plate
10 µl/minsuperfusion
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Placenta explant preparation
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Placenta explant models
long term culturesuperfusion
short term culturenormal plate
automatizedpunch
explant
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Placenta explant toxicity assessment
• all common methods
after incubation with test substances
(e.g. immunohistochmistry, PCR, ….omics, sequencing,
single cell analyses, immunodetection)
• cytotoxicty
• hormonal disruption
• inflammation reactions
• metabolic changes