New microfluidic device mimics the exchange of nutrients between mother and fetus infected with placental malaria

placental malaria as a result Plasmodium falciparum The infection can lead to serious complications for both the mother and the baby. Placental malaria causes approximately 200,000 newborn deaths each year, mainly due to low birth weight, as well as 10,000 maternal deaths. Placental malaria is caused by red blood cells infected with parasites that attach within the tree-like branch structures that make up the placenta.

The search for the human placenta is an empirical challenge due to ethical considerations and the inaccessibility of live organs. The anatomy of the human placenta and the structure 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’s College of Engineering and Computer Science and Schmidt College of Medicine have developed an on-chip placenta model that simulates nutrient exchange between the fetus and the mother under the influence of placental malaria. Combining microbiology and engineering techniques, this new 3D model uses a single microfluidic chip to study the complex processes that occur in malaria-infected placentas as well as other diseases and conditions associated with the placenta.

The placenta on the chip mimics blood flow and the microenvironment of the malaria-infected placenta mimics this flow state. Using this method, researchers closely examine the process that occurs when infected red blood cells interact with blood vessels in the placenta. This tiny device enables them to measure the spread of glucose across the typical placental barrier and the effects of blood infected with Plasmodium falciparum It can adhere to the surface of the placenta using a placental-expressing molecule called CSA.

For the study, trophoblasts or cells of the outer layer of the placenta and endothelial cells of the human umbilical vein were cultured on opposite sides of the extracellular matrix generation in a segmented microfluidic system, forming a physiological barrier between the co-flow tubular structure to mimic a streamlined shape. The maternal-fetal interface in the chorionic villi.

The results are published in Scientific ReportsAnd the showed that CSA-binding erythrocytes added resistance to the placental barrier mimicking glucose perfusion and reduced glucose transport across this barrier. Comparison of the rate of glucose transport across the placental barrier in uninfected or uninfected conditions Plasmodium falciparum The influx of infected blood to the cells of the outer layer helps to better understand this important aspect of placental malaria and can be used as a model to study treatment modalities for placental malaria.

Despite advances in biological analysis and live cell imaging, interpretation of transport across the placental barrier remains challenging. This is because placental nutrient transport is a complex problem involving multiple cell types, multilayered structures, as well as coupling between cell consumption and diffusion across the placental barrier. Our technology supports the formation of micro-engineered placental barriers that mimic circulation, providing alternative methods of testing and screening.”

Sarah E. Doe, Ph.D., first author and associate professor, Department of Oceanography and Mechanical Engineering at FAU

Most of the molecular exchange between maternal and fetal blood occurs in the branching, tree-like structures called villus trees. Because placental malaria may only start after the start of the second trimester when the spaces between infected red blood cells and white blood cells open up, the researchers were interested in the placental model of the mother-fetus interface that formed in the second half of pregnancy.

“This study provides vital information about the exchange of nutrients between a malaria-infected mother and fetus,” said Stella Batalama, PhD, dean of the FAU School of Engineering and Computer Science. “Studying molecular transport between the maternal and fetal compartments may aid in understanding some of the pathophysiological mechanisms in placental malaria. Importantly, this new microfluidic device developed by our researchers at Florida Atlantic University could serve as a model for other diseases related to the placenta.”

The study’s co-authors are Babak Musavati, Ph.D., a recent graduate of the Faculty of Engineering and Computer Science at FAU; and Andrew Olenikov, PhD, 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.

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Journal reference:

Mosavati, b. et al. (2022) Three-dimensional microfluidic-assisted modeling of glucose transport in placental malaria. Scientific Reports. doi.org/10.1038/s41598-022-19422-y.

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