Placenta-on-a-Chip Sensing Platform to Study Placental Malaria

用于研究胎盘疟疾的胎盘芯片传感平台

• 批准号: 9373330
• 负责人: E Du
• 金额: $ 21.69万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-14 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9373330
• 关键词: Address; Adhesions; Animals; Antibodies; Biosensing Techniques; Blood; Blood Circulation; Blood capillaries; Blood flow; Cell Adhesion Molecules; Cell Culture Techniques; Cells; Data; Diffusion; Disease; Endothelium; Erythrocytes; Event; Falciparum Malaria; Fetal Development; Fetal Growth; Fetal Growth Retardation; Functional disorder; Future; Glucose; Goals; Human; Human Biology; Immunofluorescence Microscopy; Impairment; In Situ; In Vitro; Infant Mortality; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Intervention; LDL-Receptor Related Protein 2; Link; Low Birth Weight Infant; Malaria; Measurement; Measures; Mediating; Microfluidics; Microscopy; Modeling; Molecular; Monitor; Nutrient; Organ; Oxygen; Pathogenesis; Pathologic; Pathology; Perfusion; Pharmacotherapy; Physiological; Physiology; Placenta; Placental Biology; Plasmodium falciparum; Preclinical Drug Evaluation; Pregnancy; Pregnancy Outcome; Proteins; Resolution; Side; Signal Transduction; Structure; Surface; Syncytiotrophoblast; System; Techniques; Technology; Testing; Time; Trypsin; Work; base; capillary; cytokine; cytotrophoblast; detection of nutrient; electric impedance; fetal; improved; in vivo; insight; macrophage; microscopic imaging; novel; novel strategies; novel therapeutics; nutrition; placental infection; placental malaria; prevent; prototype; response; temporal measurement; tool; trophoblast

Project Summary/Abstract The primary goal of this project is to develop in vitro placental model with real-time sensing capabilities for study of human placental pathologies, using microfluidics, placenta-on-a-chip and microsensing technologies. We will demonstrate the capabilities of the proposed platform with Plasmodium falciparum placental malaria model. Important pathological events, including sequestration of infected erythrocytes (IE), placental trophoblast inflammatory and perfusion responses will be evaluated and monitored in real time and under flow conditions. To accomplish this goal, we propose two specific aims to prototype and evaluate this platform. Aim 1 is to develop a 2D placental model with impedimetric sensing and evaluate two pathological events of placental malaria, including IE sequestration and trophoblast inflammatory responses in real time. The analysis will include microscopic imaging of IE sequestration and corresponding electrical impedance sensing of IE passage and adhesion, as well as electrical impedance sensing of trophoblast integrity combined with measurements of cytokines levels and immunofluorescence microscopy to test for trophoblast inflammatory responses. Aim 2 is to develop a 3D placental model with electrochemical sensing for oxygen and glucose perfusion through the placental barrier. Pathological events of IE sequestration and impacted placental barrier perfusion response will be associated with the measured parameters. Furthermore, in both aims, we will evaluate the influences of anti- adhesion interventions, including anti-PfEMP1 antibodies and known anti-adhesion molecules on those pathological events. Proof-of-the-concept study of this placental sensing platform using placental malaria model is essential for future studies to elucidate the molecular details of placental malaria pathology and other placental pathologies, as well as to develop novel therapeutics to prevent or alleviate placental inflammatory and adverse perfusion responses.

项目概要/摘要 该项目的主要目标是开发具有实时传感功能的体外胎盘模型以供研究 使用微流体、胎盘芯片和微传感技术来研究人类胎盘病理学。我们将 通过恶性疟原虫胎盘疟疾模型展示所提出的平台的功能。 重要的病理事件，包括感染红细胞（IE）、胎盘滋养层的隔离 将在流动条件下实时评估和监测炎症和灌注反应。 为了实现这一目标，我们提出了两个具体目标来原型设计和评估该平台。目标1是发展 具有阻抗传感的 2D 胎盘模型，并评估胎盘疟疾的两种病理事件， 包括实时 IE 隔离和滋养层炎症反应。分析将包括 IE 隔离的显微成像以及 IE 通道的相应电阻抗传感 粘附，以及滋养层完整性的电阻抗传感与测量相结合 细胞因子水平和免疫荧光显微镜检测滋养层炎症反应。目标 2 是 开发具有电化学传感功能的 3D 胎盘模型，通过 胎盘屏障。 IE 隔离和影响胎盘屏障灌注反应的病理事件将 与测量的参数相关联。此外，在这两个目标中，我们将评估反 粘附干预措施，包括抗 PfEMP1 抗体和已知的抗粘附分子 病理事件。使用胎盘疟疾模型对该胎盘传感平台进行概念验证研究 对于未来的研究阐明胎盘疟疾病理学和其他胎盘疟疾的分子细节至关重要 病理学，以及开发新的疗法来预防或减轻胎盘炎症和不良反应 灌注反应。