Department of Ocean and Mechanical Engineering, Florida Atlantic University, Boca Raton, FL, 33431, USA.
Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.
Sci Rep. 2022 Sep 10;12(1):15278. doi: 10.1038/s41598-022-19422-y.
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.
人类胎盘是一个关键器官，介导胎儿和母亲之间营养物质、氧气和废物的交换。由恶性疟原虫引起的胎盘疟疾 (PM) 每年导致多达 20 万新生儿死亡，主要原因是低出生体重，以及 1 万例母亲死亡。在这项工作中，开发了一种胎盘芯片模型，以模拟 PM 影响下胎儿和母亲之间的营养物质交换。在该模型中，滋养层细胞（面向感染或未感染的血液，模拟母体血液，称为“滋养层侧”）和人脐静脉内皮细胞（面向未感染的血液，模拟胎儿血液，称为“内皮侧”）在腔室微流控系统中位于细胞外基质凝胶的相对侧培养，在共流管状结构之间形成生理屏障，模拟胎盘绒毛中简化的母体-胎儿界面。研究了通过黏附到滋养层细胞表面表达的硫酸软骨素 A（CSA）上的细胞黏附作用来隔离感染红细胞（IEs）对葡萄糖跨胎盘屏障转移效率的影响，这是 PM 的一个关键特征。为了在屏障上创建葡萄糖梯度，将具有较高葡萄糖浓度的未感染红细胞或 IE 悬浮液引入“滋养层侧”，并将具有较低葡萄糖浓度的培养基引入“内皮侧”。在流动条件下，监测内皮通道中葡萄糖水平对滋养层通道中 CS2 系寄生虫感染的 CSA 结合 IE 的反应。未感染的红细胞作为阴性对照。结果表明，CSA 结合的 IEs 增加了模拟胎盘屏障对葡萄糖灌注的阻力，并降低了葡萄糖通过该屏障的转移。这项研究的结果可用于更好地理解 PM 病理学，并开发有助于研究 PM 潜在治疗方法的模型。
