Macrophage-Endothelial Crosstalk in Placental Angiogenesis

During pregnancy, the placenta (or so-called afterbirth) establishes a connection between mother and child and transports oxygen and nutrients to the child. In order to fulfil this transport function, it is important that sufficient blood vessels are build up within the placenta, and that these vessels are properly working. Those cells lining inside of the vessel walls are called endothelial cells. In pregnant women suffering from pre-eclampsia (also pregnancy toxemia) changes in number and function of placental vessels occurs. This leads to often life-threatening- hypertension in the mother. Moreover, nutrient transport across the placenta is changed, leading to fetal growth restriction, which affects the childs long-term health. Therefore, it is important to understand those mechanisms underlying the formation of placental blood vessels. However, not only endothelial cells contribute to vessel formation; macrophages, cells actually belonging to the immune system, also have been suggested to contribute to vessel formation. Cancer research has demonstrated that in tumors, macrophages and endothelial cells communicate with each other; this communication causes the formation of new blood vessels within the tumor, ensuring its nutrient supply and growth. Although parallels in the development of placenta and tumors exist, little is known about the dialogue between macrophages and endothelial cells of the placenta and how it might contribute to the formation of new placental vessels. Therefore, investigation of these placental cells and their interaction is the topic of the current study. Scientists at the Medical University of Graz suggest that the same interaction partners mediating communication between macrophages and endothelial cells in tumors, might also mediate interaction of these cells in placenta. To confirm this concept, the two cell types are isolated from placenta and cultivated together under bodily conditions, and those proteins mediating interaction between the two cell types will be identified. Furthermore, vessel formation upon co-culture of both cell types will be observed directly within a gel-like artificial vessel bed, and pictured using a 3D approach. As it is assumed that pre-eclampsia disturbs the communication between macrophages and endothelial cells, placentae from diseased patients will be investigated as well. The study at- hand aims to provide the missing proof that placental macrophages and endothelial cells interact, and support a better understanding of vessel formation in health and disease. In long-term, the obtained results will offer points of intervention to modulate vessel formation, and indirectly maternal and fetal health.