Organ-on-a-Chip Network & Emulate Proof of Concept Award
Development of a human placental artery-on-a-chip to study placental vascular function in reproductive toxicology and pregnancy diseases
SummaryDuring pregnancy, appropriate regulation of the blood vessels of the placenta is essential to supply sufficient nutrients for healthy life of the developing baby before and after birth. Drugs and other potential harmful molecules present in the maternal blood could alter the function of placental blood vessels to nourish the fetus, since they cross the placenta, with detrimental effects on the fetus. In up to 5–10% of pregnancies, the baby grows slow or stops to grow when it is in the mother’s womb.
It is now clear that the quality of life in utero crucially determines the quality of fetal development and further predisposes the newborn to long-term health. Current laboratory experimental approaches to study placental vascular function have limitations. Some involve the use of animal models to study the effect of maternal factors on the placental vasculature. Other methods use only one type of cell, and do not show how the different cellular components of the placental blood vessels communicate with one another. Importantly, in current experiments where blood vessels are freshly collected from normal pregnancy, the absence of long term exposure to an environmental change does not allow the cells of the tissue to alter their behaviour, as they might in the womb across a longer time period. An experimental design with longer experimental exposure, closer to exposure times in pregnancy, is required to study the time-dependent effects of molecules and other environmental conditions on placental vascular function.
Herein, we propose a model of a human placental artery-on-a-chip, to allow us to study the effect of circulating maternal factors on key components of the artery: endothelial and smooth muscle cells, which work together in the body to control blood flow and nutrient supply by modulating the contraction of the vessel wall. These cells will be isolated from human placentas and grown together inside tiny plastic chambers, perfused with artificial blood. Cell-to-cell responses to drugs, pollutants and other environmental changes linked to diseases will be studied to realise the effects of an altered maternal environment on placental function.
Preliminary data generated in this project will support future grant applications. If successful, this new model could be used in our laboratory to advance our basic understanding of interactions between endothelial and smooth muscle cells; and provide new and cheaper methods in human reproductive toxicology testing of medicines and environmental chemicals. Additionally, by using cells isolated according to pregnancy pathologies and demographic parameters, the assessment of differential cell to-cell interaction responses will help to gain an understanding of the effects of altered maternal environment on the function of the placenta in pathological conditions, and help clinicians to develop personalised care in pregnancy.