Development of a BBB model to study transendothelial cell migration
开发 BBB 模型来研究跨内皮细胞迁移
基本信息
- 批准号:8537506
- 负责人:
- 金额:$ 47.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAnti-Inflammatory AgentsAnti-inflammatoryArtsBiologicalBlood - brain barrier anatomyBlood VesselsBlood capillariesBrainBrain DiseasesCell LineCharacteristicsClinicalCoculture TechniquesContractsDataDevelopmentDiseaseDrug resistanceEconomicsEndothelial CellsEpilepsyExperimental DesignsExtravasationFee-for-Service PlansFiberHumanImmune responseIn VitroInflammatoryKnowledgeLeukocyte TraffickingLeukocytesMechanicsMediationModalityModelingMultiple SclerosisNeurogliaPathologicPatternPerformancePericytesPermeabilityPharmaceutical PreparationsPharmacological TreatmentPharmacologyPhasePhysiologicalPhysiologyProcessProgress ReportsPropertyProtocols documentationPublishingRecording of previous eventsReproductionResearch PersonnelRestRodentRoleScanning Electron MicroscopySideSignal TransductionSmall Business Technology Transfer ResearchSmooth Muscle MyocytesStimulusStretchingSystemTest ResultTestingTractionbasecapillarycell motilitychemokineclinically relevantcommercializationdesigndrug developmentdrug testingdrug use screeninghemodynamicsimprovedin vitro Modelinsightmigrationmonocytenervous system disordernovelpre-clinicalprototyperesearch and developmentresearch studyresponsescale upshear stresssoundsuccesstherapeutic targetvenule
项目摘要
DESCRIPTION (provided by applicant): Reproducing in vitro the physiological characteristics of brain vascular segments represents a critical issue. Adequate modeling of the cerebrovasculature could significantly help understand the mechanisms and improve the pharmacology of disease where a role for leukocytes migrating across the cerebrovasculature is demonstrated. Thanks to the previous support (Phase I) we were able to prototype and test drive a new dynamic in vitro model of the BBB (DIV- BBB) permissive for leukocyte extravasation. Our initial effort aimed at piercing hollow fibers in a reproducible manner; the results were recently published. We found that manually perforated hollow fibers allow leukocytes passage across the BBB in response to pro-inflammatory stimuli and hemodynamic changes. We were also able to produce a capillary-venule segment by varying the rheological parameters (e.g., changing the shear stress) of the system. In addition we recently developed a system to mechanically "stretch" the hollow fibers increasing the pore size up to the physiologically relevant size of ~5 ¿m. Controlled traction was applied to the end of the fibers and scanning electron microscopy showed enlarged pores within the stretched fiber. To further the commercial opportunity afforded by this new BBB model, we propose the following Phase II Specific Aims: To optimize the performance of a dynamic in vitro capillary-venules model of the brain cerebrovasculature permissive for leukocyte extravasation. To determine the pattern of leukocytes extravasation in control and diseased capillary-venules segments composed of fibers with different transmural permeability properties (from Aim 1). To compare the results obtained using these DIV- BBB models to other state-of-art in vitro BBB models. We will initially tailor the use of the DIV capillary-venules system to multiple sclerosis and epilepsy research and drug development. We have assembled a multi-disciplinary team of investigators and experts in the field of leukocyte migration across the cerebrovasculature. Additional clinically relevant venues are detailed in the Commercialization Plan. Given our preliminary results and the confirmatory progress report described in detail in this application, and given the fact that i the meantime development of new drugs has remained a major issue in the treatment of neurological diseases, we believe that the combination of a strong record of accomplishment and sound experimental design aimed at improving drug development are fundamental aspects of this Phase 2 proposal.
描述(由申请人提供):脑血管分段的体外特征是对脑血管造成的适当建模,有助于这些机制,并改善了对白血病细胞的药理学,在此阶段迁移了跨大脑的白血病细胞(阶段) i)原型驱动了BBB(DIV-BBB)的新动态体外模型。变化我们还能够通过改变系统的流变参数(例如剪切应力)来产生毛细血管 - 片段。到他的生理相关大小〜5€ m。大脑脑血管造成的脑血管细胞的渗入和具有不同的透射透过透气性特性的纤维性毛细管片段,以比较使用THELS获得的结果与其他最先进的体外BBB模型。 - 多发性硬化症和癫痫病的研究和药物开发。对神经系统疾病的治疗,我们认为旨在改善开发的Accoment D声音实验设计的强大记录的组合是该第2阶段建议的基本方面。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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DAMIR JANIGRO其他文献
DAMIR JANIGRO的其他文献
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{{ truncateString('DAMIR JANIGRO', 18)}}的其他基金
Drug brain biotransformation in human refractory epilepsy
人类难治性癫痫的药物脑生物转化
- 批准号:
8715418 - 财政年份:2012
- 资助金额:
$ 47.07万 - 项目类别:
Drug brain biotransformation in human refractory epilepsy
人类难治性癫痫的药物脑生物转化
- 批准号:
8545915 - 财政年份:2012
- 资助金额:
$ 47.07万 - 项目类别:
Development of a BBB model to study transendothelial cell migration
开发 BBB 模型来研究跨内皮细胞迁移
- 批准号:
8314680 - 财政年份:2012
- 资助金额:
$ 47.07万 - 项目类别:
Neurovascular Unit on a Chip: Chemical Communication, Drug and Toxin Responses
芯片上的神经血管单元:化学通讯、药物和毒素反应
- 批准号:
8516129 - 财政年份:2012
- 资助金额:
$ 47.07万 - 项目类别:
Drug brain biotransformation in human refractory epilepsy
人类难治性癫痫的药物脑生物转化
- 批准号:
8436699 - 财政年份:2012
- 资助金额:
$ 47.07万 - 项目类别:
Neurovascular Unit on a Chip: Chemical Communication, Drug and Toxin Responses
芯片上的神经血管单元:化学通讯、药物和毒素反应
- 批准号:
8768903 - 财政年份:2012
- 资助金额:
$ 47.07万 - 项目类别:
Serum markers of football-related brain concussions: a pilot study
足球相关脑震荡的血清标志物:一项试点研究
- 批准号:
8321985 - 财政年份:2011
- 资助金额:
$ 47.07万 - 项目类别:
Serum markers of football-related brain concussions: a pilot study
足球相关脑震荡的血清标志物:一项试点研究
- 批准号:
8229390 - 财政年份:2011
- 资助金额:
$ 47.07万 - 项目类别:
Development of a BBB Model to Study Transendothelial Cell Migration
开发 BBB 模型来研究跨内皮细胞迁移
- 批准号:
8203729 - 财政年份:2010
- 资助金额:
$ 47.07万 - 项目类别:
Development of a BBB Model to Study Transendothelial Cell Migration
开发 BBB 模型来研究跨内皮细胞迁移
- 批准号:
7998687 - 财政年份:2010
- 资助金额:
$ 47.07万 - 项目类别:
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