Novel microfluidic device mimics nutrient exchange between mother and fetus affected by placental malaria

Novel microfluidic device mimics nutrient exchange between mother and fetus affected by placental malaria

Placental malaria resulting from Plasmodium falciparum infection can lead to serious complications for mother and child. Each year, placental malaria causes nearly 200,000 newborn deaths, primarily due to low birth weight, as well as 10,000 maternal deaths. Placental malaria results from parasite-infected red blood cells that become stuck in tree-like branch structures that make up the placenta.

Research on the human placenta is experimentally challenging due to ethical considerations and the inaccessibility of the living organs. The anatomy of the human placenta and the architecture of the maternal-fetal interface, such as: B. between maternal and fetal blood, are complex and cannot easily be reconstructed in their entirety using modern in vitro models.

Researchers from Florida Atlantic University's College of Engineering and Computer Science and Schmidt College of Medicine have developed a placenta-on-a-chip model that mimics nutrient exchange between the fetus and mother under the influence of placental malaria. Combining microbiology with engineering technologies, this novel 3D model uses a single microfluidic chip to study the intricate processes that take place in a placenta infected with malaria, as well as other placenta-related diseases and pathologies.

Placenta-on-a-Chip simulates blood flow and mimics the microenvironment of the malaria-infected placenta in this flow state. Using this method, researchers study exactly the process that occurs when the infected red blood cells interact with the vessels of the placenta. This microdevice allows them to measure glucose diffusion 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 the placenta-expressed molecule called CSA.

For the study, placental trophoblasts or outer layer cells 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 parallel tubular structure to mimic a simplified maternal-fetal interface Placental villi.

The results, published in Scientific Reports, showed that CSA-binding infected RBCs added resistance to the simulated placental barrier to glucose perfusion and reduced glucose transfer across this barrier. The comparison between the rate of glucose transport across the placental barrier under conditions when uninfected or P. falciparum-infected blood flows to outer layer cells helps to better understand this important aspect of placental malaria pathology and could potentially be used as a model to study methods of treating placental malaria.

Despite advances in biosensing and live-cell imaging, interpreting transport across the placental barrier remains a challenge. This is because nutrient transport across the placenta is a complex problem involving multiple cell types, multilayered structures, and the coupling between cell consumption and diffusion across the placental barrier. Our technology supports the formation of micro-engineered placental barriers and mimics blood circulation, providing alternative approaches to testing and screening.”

Sarah E. Du, Ph.D., Senior Author and Associate Professor, Department of Ocean and Mechanical Engineering at FAU

Most of the molecular exchange between maternal and fetal blood occurs in the branching tree-like structures called villous trees. Since placental malaria can only begin after the start of the second trimester, when the intervillous space opens to infected red blood cells and white blood cells, the researchers were interested in the placental model of the mother-fetal interface, which is formed in the second half of pregnancy.

“This study provides important information about the exchange of nutrients between mother and fetus affected by malaria,” said Stella Batalama, Ph.D., dean, FAU College of Engineering and Computer Science. "Studying molecular transport between maternal and fetal compartments may help understand some of the pathophysiological mechanisms in placental malaria. Importantly, this novel microfluidic device developed by our researchers at Florida Atlantic University could serve as a model for other placenta-related diseases."

Co-authors of the study 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 at 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.

Source:

Florida Atlantic University

Reference:

Mosavati, B., et al. (2022) 3D microfluidics-assisted modeling of glucose transport in placental malaria. Scientific reports. doi.org/10.1038/s41598-022-19422-y.

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