Abstract
The human placenta is a critical organ, mediating the exchange of nutrients, oxygen, and waste products between fetus and mother. Placental malaria (PM) resulted from Plasmodium falciparum infections causes up to 200 thousand newborn deaths annually, mainly due to low birth weight, as well as 10 thousand mother deaths. In this work, a placenta-on-a-chip model is developed to mimic the nutrient exchange between the fetus and mother under the influence of PM. In this model, trophoblasts cells (facing infected or uninfected blood simulating maternal blood and termed "trophoblast side") and human umbilical vein endothelial cells (facing uninfected blood simulating fetal blood and termed "endothelial" side) are cultured on the opposite sides of an extracellular matrix gel in a compartmental microfluidic system, forming a physiological barrier between the co-flow tubular structure to mimic a simplified maternal-fetal interface in placental villi. The influences of infected erythrocytes (IEs) sequestration through cytoadhesion to chondroitin sulfate A (CSA) expressed on the surface of trophoblast cells, a critical feature of PM, on glucose transfer efficiency across the placental barrier was studied. To create glucose gradients across the barrier, uninfected erythrocyte or IE suspension with a higher glucose concentration was introduced into the "trophoblast side" and a culture medium with lower glucose concentration was introduced into the "endothelial side". The glucose levels in the endothelial channel in response to CSA-adherent erythrocytes infected with CS2 line of parasites in trophoblast channel under flow conditions was monitored. Uninfected erythrocytes served as a negative control. The results demonstrated that CSA-binding IEs added resistance to the simulated placental barrier for glucose perfusion and decreased the glucose transfer across this barrier. The results of this study can be used for better understanding of PM pathology and development of models useful in studying potential treatment of PM.