2019 Call: Engineering a novel cell-based model for assessing materno-fetal drug transfer during pregnancy

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Project OC-2019-019

The human placenta is a vital organ that acts as a barrier between the circulation of the mother and the growing fetus. It represents the interface between specialized placental cells called trophoblasts and fetal endothelial cells of the micro-vessels. Together these two tightly polarized cell layers perform crucial functions such as nutrient transport to the fetus or production of hormones.

As an in vitro screening model for monitoring materno-fetal drug transfer is urgently needed, we propose to develop and validate a novel 3D-cell culture system which incorporates both of these crucial cell types. Primary cells isolated from human placenta and umbilical vein will be used to create a functional in vitro co-culture perfusion model for simulating the in vivo situation at the maternal-fetal interface. The concept is innovative in this area of research, especially as we aim to use exclusively primary cells in a co-culture model, an approach which is known to present a higher degree of physiology than immortalized cell lines. The combination of optimal cell isolation methods, special media containing defined growth factors and culture chambers designed for studying drug transport represent a highly creative solution to a real need in our society. The model will be cheap to apply and rapid with a time frame of just one week needed for appropriate synchronized growth of the two cell types. Most importantly, it can provide a safe initial screening method for new drugs indicating whether they reach the fetal circulation and might exert toxic effects to the unborn.

“In the currently applied drug screening approaches several hundreds of animals per drug are used to investigate potentially toxic effects on the developing fetus,” Albrecht explains. “A reproducible and validated human cell based model which is approved by the regulatory agencies may serve as a primary screening model in the future. Thereby the use of numerous animals will be prevented and the overt limitations of animal models will be overcome.”

Prof. Christiane Albrecht
Institute of Biochemistry and Molecular Medicine, University of Bern

Prof. František Štaud
Pharmaceutical Faculty, Charles University, Hradec Kralove, Czech Republic

Dr Chennakesava Cuddapah
Curio Biotech SA, Visp, Switzerland