Placental malaria following Plasmodium falciparum infections can lead to serious complications for both mother and child. Each year, placental malaria causes almost 200,000 newborn deaths, mainly due to low birth weight, as well as 10,000 maternal deaths. Placental malaria results from parasite-infected red blood cells that get stuck in tree-like branch structures that make up the placenta.
Research on the human placenta is experimentally difficult due to ethical considerations and the inaccessibility of living organs. The anatomy of the human placenta and the architecture of the maternal-fetal interface, such as between maternal and fetal blood, are complex and cannot be easily reconstructed in their entirety using modern in vitro models.
Researchers from Florida Atlantic University College of Engineering and Computer Science and Schmidt College of Medicine have developed an on-chip placenta model that mimics the exchange of nutrients between fetus and mother under the influence of placental malaria . Combining microbiology with engineering technologies, this new 3D model uses a single microfluidic chip to study the complex processes that take place in the placenta infected with malaria as well as other placenta-related diseases and pathologies.
The on-chip placenta simulates blood flow and mimics the microenvironment of the malaria-infected placenta in this flow condition. Using this method, researchers are looking closely at the process that takes place when infected red blood cells interact with the placental vasculature. This microdevice allows them to measure the diffusion of glucose across the modeled placental barrier and the effects of blood infected with a P. falciparum line that can adhere to the surface of the placenta using a molecule expressed in the placenta called CSA.
For the study, trophoblasts or cells from the outer layer of the placenta and human umbilical vein endothelial cells were cultured on opposite sides of an extracellular matrix gel in a compartmentalized microfluidic system, forming a physiological barrier between the co-flow tubular structure to mimic a simplified maternal-fetal interface in the placental villi.
Results, published in Scientific reports, demonstrated that CSA-binding infected erythrocytes added resistance to the simulated placental barrier for glucose infusion and decreased glucose transfer across this barrier. The comparison between the rate of glucose transport across the placental barrier under uninfected or P. falciparum infected blood flows to outer layer cells help to better understand this important aspect of placental malaria pathology and could potentially be used as a model to investigate ways to treat placental malaria.
Despite advances in biosensing and live cell imaging, the interpretation of transport across the placental barrier remains challenging. Indeed, placental nutrient transport is a complex problem that involves multiple cell types, multi-layered structures, as well as the coupling between cellular uptake and diffusion across the placental barrier. Our technology supports the formation of microengineered placental barriers and mimics blood flow, providing alternative approaches for testing and screening. »
Sarah E. Du, Ph.D., Senior Author and Associate Professor, Department of Oceanic and Mechanical Engineering, FAU
Most of the molecular exchange between maternal and fetal blood occurs in branching tree structures called villous trees. Since placental malaria may not begin until after the onset of the second trimester, when the intervillous space opens to infected red blood cells and white blood cells, researchers were interested in the placental model of the mother-fetus interface formed in the second half of pregnancy.
“This study provides vital information about the exchange of nutrients between mother and fetus affected by malaria,” said Stella Batalama, Ph.D., dean of the FAU College of Engineering and Computer Science. “The study of molecular transport between the maternal and fetal compartments can help to understand some of the pathophysiological mechanisms of placental malaria. Importantly, this new microfluidic device developed by our researchers at Florida Atlantic University could serve as a model for other placenta-related diseases.
The study’s co-authors are Babak Mosavati, Ph.D., a recent graduate of FAU’s College of Engineering and Computer Science; and Andrew Oleinikov, Ph.D., Professor of Biomedical Sciences, FAU Schmidt College of Medicine.
The research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, and the National Science Foundation.
Florida Atlantic University
Mosavati, B. et al. (2022) 3D microfluidic-assisted modeling of glucose transport in placental malaria. Scientific reports. doi.org/10.1038/s41598-022-19422-y.
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