A novel physiologically realistic microfluidic in-vitro blood-brain barrier model

一种新颖的生理真实微流控体外血脑屏障模型

• 批准号: 8469865
• 负责人: BALABHASKAR PRABHAKARPANDIAN
• 金额: $ 61.9万
• 依托单位: CFD RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469865
• 关键词: Animal Model; Apical; Astrocytes; Basic Science; Biochemical; Biological; Biological Assay; Biology; Blood - brain barrier anatomy; Blood flow; Brain; Cell Line; Cells; Characteristics; Chemicals; Coculture Techniques; Collaborations; Conditioned Culture Media; Connexins; Data; Devices; Drug Delivery Systems; Drug usage; Electrical Resistance; Electrodes; Endothelial Cells; Engineering; Evaluation; Failure; Generations; Imagery; Immigration; In Vitro; Inflammatory; Internet; Journals; Knowledge; Leukocytes; Libraries; Measurement; Measures; Microcirculation; Microfluidic Microchips; Microfluidics; Modeling; Monitor; Neuraxis; Neuroglia; Neurologic; Neurons; Optics; Pediatric Hospitals; Penetration; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiological; Plastics; Process; Publications; Rattus; Reagent; Research; Research Personnel; Saint Jude Children' s Research Hospital; Scientist; Side; Simulate; Staging; Techniques; Technology; Testing; Therapeutic Effect; Therapeutic Human Experimentation; Tight Junctions; Time; Toxic effect; Universities; Up-Regulation; Visual; Work; base; cost; data modeling; design; drug candidate; drug development; drug discovery; electrical measurement; immortalized cell; improved; in vitro Model; in vivo; instrumentation; interest; lithography; meetings; migration; novel; novel strategies; particle; protein expression; receptor expression; screening; shear stress; symposium; therapeutic development

DESCRIPTION (provided by applicant): The overall objective of this study is to develop a novel in vitro microfluidic platform to test a drug or delivery vehicle's ability to permeate the Blood-Brain Barrier (BBB). In contrast to current in-vitro models, our proposed device, SIM-BBB, comprises of a microfluidic two-compartment chamber. The chamber is designed in such a way as to permit visualization-friendly evaluation of transport/permeation under appropriate microcirculatory size and flow conditions, while simultaneously simplifying device fabrication. The apical side is seeded with endothelial cells and the basolateral side supports glial cell co-cultures. The increased physiological realism substantially improves BBB characteristics including formation of tight junctions and expression of relevant transporters. The new platform offers greater throughput, increased library coverage, lower cost, rapid turnaround times and increased mechanistic knowledge benefiting drug discovery efforts. In Phase I, the first generation microfluidic SIM-BBB device was designed and fabricated using soft lithography. Brain endothelial cells were cultured in the microfluidic constructs with a perfusate of astrocyte conditioned media. Biochemical analysis showed upregulation of tight junction molecules while optical analysis showed intactness of the BBB in the microfluidic device. Finally, transporters assay was successfully demonstrated in the device. Phase II efforts will focus on optimization of the microfluidic device for enhanced physiological fidelity. Electrodes will be integrated for non-visual monitoring of the endothelial cell layers and tight junction formation via trans-endothelial electrical resistance (TEER) measurements. Finally, the developed technology will be demonstrated for diverse applications including drug penetration studies and leukocyte migration under inflammatory conditions. A multi-disciplinary partnership with expertise in engineering and biology has been assembled for successful completion of the project.

描述（由申请人提供）：