Functional 3D tissue-engineering models of the cerebrovasculature incorporating stem cell-derived brain microvascular endothelial cells, pericytes, and astrocytes
脑血管系统的功能性 3D 组织工程模型,包含干细胞来源的脑微血管内皮细胞、周细胞和星形胶质细胞
基本信息
- 批准号:10328888
- 负责人:
- 金额:$ 33.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAchievementAddressAdultAdvanced DevelopmentAstrocytesBenchmarkingBloodBlood - brain barrier anatomyBlood VesselsBlood capillariesBrainBrain DiseasesCellsCentral Nervous System DiseasesCerebrovascular systemChemistryComplexDevelopmentDiseaseDisease ProgressionDrug Delivery SystemsEndothelial CellsFunctional disorderGene DeliveryGenerationsGoalsHealthHumanImmuneMethodsModelingMorphologyNervous system structureNeuronsNeurosciences ResearchNutrientOxidative StressPericytesPhenotypePhysiologicalProblem SolvingRoleSourceStressStructureSystemTimeTissue EngineeringToxic effectToxinTranslationsUmbilical veinVascular SystemVascularizationWorkarteriolebrain endothelial cellcerebral microvasculatureclinically relevanthuman modelinduced pluripotent stem cellmicrophysiology systemnetwork modelsneurogenesisneuroinflammationneurotoxicitynew technologynovel therapeuticspathogenpostcapillary venulepreventrepairedresponseself organizationspecific biomarkersstem cell biologystem cell technologystem cellsthree dimensional cell culturetoolvascular tissue engineeringvenule
项目摘要
Project Summary
!
The neurovasculature supplies nutrients to the 100 billion neurons in the adult human brain via a 600 km
network of capillaries and microvessels. As the interface between the brain and the vascular system, the
blood-brain barrier, which includes the neurovasculature, is responsible for regulating the brain
microenvironment by preventing fluctuations in chemistry, transport of immune cells, and the entry of toxins
and pathogens. At the same time, almost all diseases of the brain are associated with disruption or
dysfunction of the neurovasculature, which leads to entry of blood components, immune cells, and pathogens
into the brain, and ultimately causes neuroinflammation, oxidative stress, and neurotoxicity. Functional human
models have the potential to address many unresolved questions associated with the role of the
neurovasculature in health and disease, and in developing more complex models of the human nervous
system that will ultimately contribute towards the realization of integrated multicellular systems.
There are two major challenges to developing physiologically-relevant, tissue-engineered models of the human
neurovasculature: (1) a source of relevant cells, and (2) 3D cell culture methods to build the model. Stem cell
technology provides a solution to providing a reliable source of human, brain-specific cells, a long-standing
barrier to developing blood-brain barrier models. Similarly, advances in tissue engineering provide the tools for
self-organization of perfusable vascular networks. Solving these problems will have significant impact on
neuroscience research, elucidating mechanisms of central nervous system diseases, and in the development
and translation of new therapies and technologies. In Aim 1 we will characterize the phenotype and barrier
function of brain microvessels under quiescent conditions and in response to activation/stress. In Aim 2 we will
develop and characterize brain-specific capillary networks. In Aim 3 we will integrate pericytes and astrocytes
into our models. These models will enable a broad range of applications, including fundamental studies of
neurogenesis, vascularization, and development, and mechanistic studies of disease progression, treatment,
repair, drug and gene delivery, and toxicity.
项目概要
!
神经血管系统通过 600 公里的管道为成人大脑中的 1000 亿个神经元提供营养
毛细血管和微血管网络。作为大脑和血管系统之间的接口,
血脑屏障,包括神经血管系统,负责调节大脑
通过防止化学波动、免疫细胞运输和毒素进入来改善微环境
和病原体。与此同时,几乎所有的大脑疾病都与大脑的破坏或破坏有关。
神经血管功能障碍,导致血液成分、免疫细胞和病原体进入
进入大脑,最终导致神经炎症、氧化应激和神经毒性。功能人
模型有潜力解决许多与角色的作用相关的未解决问题
健康和疾病中的神经脉管系统,以及开发更复杂的人类神经模型
最终将有助于实现集成多细胞系统。
开发生理相关的人体组织工程模型面临两大挑战
神经血管系统:(1) 相关细胞的来源,以及 (2) 构建模型的 3D 细胞培养方法。干细胞
技术提供了一种解决方案,可以提供人类大脑特异性细胞的可靠来源,这是一种长期存在的
开发血脑屏障模型的障碍。同样,组织工程的进步提供了工具
可灌注血管网络的自组织。解决这些问题将产生重大影响
神经科学研究,阐明中枢神经系统疾病的机制,并在发展
以及新疗法和技术的转化。在目标 1 中,我们将描述表型和屏障的特征
脑微血管在静止条件下的功能以及对激活/应激的反应。在目标 2 中,我们将
开发并表征大脑特定的毛细血管网络。在目标 3 中,我们将整合周细胞和星形胶质细胞
进入我们的模型。这些模型将实现广泛的应用,包括基础研究
神经发生、血管形成和发育,以及疾病进展、治疗的机制研究,
修复、药物和基因传递以及毒性。
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)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Peter C Searson其他文献
Peter C Searson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Peter C Searson', 18)}}的其他基金
Elucidating the role of pericytes in angiogenesis in the brain using a tissue-engineered microvessel model
使用组织工程微血管模型阐明周细胞在大脑血管生成中的作用
- 批准号:
10648177 - 财政年份:2023
- 资助金额:
$ 33.85万 - 项目类别:
Mechanisms of cerebrovascular barrier dysfunction caused by APP and PSEN1 mutations and amyloid beta exposure
APP和PSEN1突变及β淀粉样蛋白暴露引起脑血管屏障功能障碍的机制
- 批准号:
10401690 - 财政年份:2021
- 资助金额:
$ 33.85万 - 项目类别:
Functional 3D tissue-engineering models of the cerebrovasculature incorporating stem cell-derived brain microvascular endothelial cells, pericytes, and astrocytes
脑血管系统的功能性 3D 组织工程模型,包含干细胞来源的脑微血管内皮细胞、周细胞和星形胶质细胞
- 批准号:
10546464 - 财政年份:2019
- 资助金额:
$ 33.85万 - 项目类别:
Functional 3D tissue-engineering models of the cerebrovasculature incorporating stem cell-derived brain microvascular endothelial cells, pericytes, and astrocytes
脑血管系统的功能性 3D 组织工程模型,包含干细胞来源的脑微血管内皮细胞、周细胞和星形胶质细胞
- 批准号:
9902557 - 财政年份:2019
- 资助金额:
$ 33.85万 - 项目类别:
An engineered platform for the study of metastasis (PQ #24)
用于研究转移的工程平台(PQ
- 批准号:
8513951 - 财政年份:2012
- 资助金额:
$ 33.85万 - 项目类别:
An engineered platform for the study of metastasis (PQ #24)
用于研究转移的工程平台(PQ
- 批准号:
8677827 - 财政年份:2012
- 资助金额:
$ 33.85万 - 项目类别:
An engineered platform for the study of metastasis (PQ #24)
用于研究转移的工程平台(PQ
- 批准号:
8852093 - 财政年份:2012
- 资助金额:
$ 33.85万 - 项目类别:
相似国自然基金
共和盆地东北部地区隆升剥蚀过程对干热岩形成就位的影响:来自低温热年代学的制约
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
朱鹮野生种群营养生态位对繁殖成就的影响及保护对策研究
- 批准号:
- 批准年份:2022
- 资助金额:54 万元
- 项目类别:面上项目
成就目标视角下建言韧性的形成机制与作用效果研究
- 批准号:72102228
- 批准年份:2021
- 资助金额:30 万元
- 项目类别:青年科学基金项目
科研人员流动与职业成就的关系研究
- 批准号:71874049
- 批准年份:2018
- 资助金额:48.0 万元
- 项目类别:面上项目
基于目标成就评量的社区中医药健康管理服务评价及优化策略研究
- 批准号:71874047
- 批准年份:2018
- 资助金额:49.0 万元
- 项目类别:面上项目
相似海外基金
Identifying human-specific neural progenitors and their role in neurodevelopment
识别人类特异性神经祖细胞及其在神经发育中的作用
- 批准号:
10662868 - 财政年份:2023
- 资助金额:
$ 33.85万 - 项目类别:
Identifying human-specific neural progenitors and their role in neurodevelopment
识别人类特异性神经祖细胞及其在神经发育中的作用
- 批准号:
10662868 - 财政年份:2023
- 资助金额:
$ 33.85万 - 项目类别:
Language Input as a Mechanism Underlying Socioeconomic Disparities in Neurocognitive Development
语言输入作为神经认知发展社会经济差异的机制
- 批准号:
10706839 - 财政年份:2023
- 资助金额:
$ 33.85万 - 项目类别: