Murine Circulating Endothelial Precursors (CEPs) and Lung Capillary Repair
小鼠循环内皮前体 (CEP) 和肺毛细血管修复
基本信息
- 批准号:7570686
- 负责人:
- 金额:$ 44.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-04-01 至 2013-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute Lung InjuryAddressAdultAffectAlveolarAlveolar CellAngiogenic FactorArtsBiological ModelsBloodBlood CirculationBlood VesselsBlood capillariesBone MarrowBreathingCell TherapyCellsCharacteristicsDataDevelopmentDifferentiation AntigensDiseaseEndothelial CellsEndotheliumEngraftmentFlow CytometryGoalsGrantGrowth FactorHematopoieticImaging TechniquesInfusion proceduresInjuryKineticsLabelLegal patentLifeLungMediatingMembraneModelingMolecularMusMyelogenousOrganellesOxygenPathway interactionsPhenotypePopulationProcessPulmonary HypertensionQuantum DotsRecruitment ActivityResearchResearch DesignResidual stateResolutionRespiratory distressRoleSeriesSignal PathwaySignal TransductionStromal Cell-Derived Factor 1StructureSurfaceTechniquesVascular Endothelial Growth Factorsbasecapillarydigital imagingfluorescence imagingimprovedinjuredlung vascular injurymolecular phenotypenew growthnovelpreclinical studyprecursor cellprogramspublic health relevancerepairedresponsetherapeutic targettraffickingtreatment strategy
项目摘要
DESCRIPTION (provided by applicant): This grant proposes preclinical studies to improve understanding of the cellular basis of vascular repair in the adult lung by a blood-derived cell population. We have identified a novel population of circulating endothelial precursors (CEPs) and discovered their potential to repair capillary segments in the murine lung by a previously undescribed angiogenic process. Based on preliminary data, the studies supported by this grant will be guided by three principal hypotheses: (i) in lung vascular injury CEPs fuse to endothelial cells, acquire an endothelial-like phenotype, and engraft into existing capillaries to repair their structure and function; (ii) BMDCs mobilized into the circulation and recruited to the injured lung make a major contribution to capillary repair by CEPs; and (iii) VEGF and SDF-11 signaling mediate the mobilization and recruitment of BMDCs to the injured lung and capillary repair by CEPs. State-of-the-art high resolution and fluorescence imaging approaches (using immunogold labels and quantum dots), and other quantitative approaches, i.e., flow cytometry analyses, will be used. The studies proposed will take advantage of genetically modified mice and a well-characterized model of capillary repair by CEPs in the lung injured by breathing high oxygen. Repair in acute lung injury and in the chronically injured lung - in which capillary networks are lost and then restored - will both be studied. Specifically, we aim to characterize the kinetics and phenotype of murine CEPs as they restore pulmonary capillaries (AIM 1); demonstrate in structural and functional studies, that include myelo-suppression and infusion of BMDCs sub-sets, a causal relationship between BMDCs and capillary repair by CEPs (AIM 2); and demonstrate that selective blockade of VEGF/VEGF-R2 and/or of SDF-11/CXCR4 signaling impair the mobilization and recruitment of BMDCs to the injured lung and capillary repair by CEPs (AIM 3). By understanding the role of CEPs in the salvage of existing capillary networks, the proposed studies should promote the development of cell-based treatment strategies for the acutely injured lung as well as the lung with established capillary loss.
PUBLIC HEALTH RELEVANCE: In life-threatening diseases such as the Pulmonary Hypertensions, or following acute lung injury leading to the development of a severe form of Acute Respiratory Distress, vascular injury destroys small blood vessels throughout the lung. Studies are designed to improve understanding of a newly identified process of spontaneous repair of these blood vessels by cells circulating in blood. Further understanding of how such circulating cells salvage existing blood vessels, or trigger growth of new ones, will promote the development of cell-based therapies to restore damaged vascular networks in the lung.
描述(由申请人提供):该资助提出临床前研究,以提高对成人肺血管修复的细胞基础的理解。我们已经确定了一种新的循环内皮前体(cep)群体,并发现它们通过先前未描述的血管生成过程修复小鼠肺部毛细血管段的潜力。基于初步数据,该基金支持的研究将以三个主要假设为指导:(i)在肺血管损伤中,cep与内皮细胞融合,获得内皮样表型,并植入现有毛细血管以修复其结构和功能;(ii) BMDCs被动员到循环中并被招募到受伤的肺部,对cep的毛细血管修复做出了重大贡献;(iii) VEGF和SDF-11信号介导cep对损伤肺和毛细血管修复的BMDCs的动员和募集。将使用最先进的高分辨率和荧光成像方法(使用免疫金标记和量子点)以及其他定量方法,即流式细胞术分析。提出的研究将利用转基因小鼠和具有良好特征的cep在高氧呼吸损伤肺中的毛细血管修复模型。急性肺损伤和慢性肺损伤(毛细血管网络丢失然后恢复)的修复都将被研究。具体来说,我们的目标是描述小鼠cep恢复肺毛细血管时的动力学和表型(aim 1);在结构和功能研究中,包括骨髓抑制和BMDCs亚群的输注,证明BMDCs与cep的毛细血管修复之间的因果关系(AIM 2);并证明选择性阻断VEGF/VEGF- r2和/或SDF-11/CXCR4信号通路会损害BMDCs对受损肺和cep修复的动员和募集(AIM 3)。通过了解cep在挽救现有毛细血管网络中的作用,拟议的研究应该促进基于细胞的治疗策略的发展,以治疗急性损伤的肺以及已经建立毛细血管损失的肺。
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 }}
ROSEMARY CRISTIAN JONES其他文献
ROSEMARY CRISTIAN JONES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('ROSEMARY CRISTIAN JONES', 18)}}的其他基金
Murine Circulating Endothelial Precursors (CEPs) and Lung Capillary Repair
小鼠循环内皮前体 (CEP) 和肺毛细血管修复
- 批准号:
7464681 - 财政年份:2008
- 资助金额:
$ 44.17万 - 项目类别:
Murine Circulating Endothelial Precursors (CEPs) and Lung Capillary Repair
小鼠循环内皮前体 (CEP) 和肺毛细血管修复
- 批准号:
8235016 - 财政年份:2008
- 资助金额:
$ 44.17万 - 项目类别:
Murine Circulating Endothelial Precursors (CEPs) and Lung Capillary Repair
小鼠循环内皮前体 (CEP) 和肺毛细血管修复
- 批准号:
7799776 - 财政年份:2008
- 资助金额:
$ 44.17万 - 项目类别:
Murine Circulating Endothelial Precursors (CEPs) and Lung Capillary Repair
小鼠循环内皮前体 (CEP) 和肺毛细血管修复
- 批准号:
8051756 - 财政年份:2008
- 资助金额:
$ 44.17万 - 项目类别:
Fi02 and Blood Vessel Formation in Adult Lung
Fi02 与成人肺中的血管形成
- 批准号:
6718423 - 财政年份:2003
- 资助金额:
$ 44.17万 - 项目类别:
Fi02 and Blood Vessel Formation in Adult Lung
Fi02 与成人肺中的血管形成
- 批准号:
6874951 - 财政年份:2003
- 资助金额:
$ 44.17万 - 项目类别:
Fi02 and Blood Vessel Formation in Adult Lung
Fi02 与成人肺中的血管形成
- 批准号:
6619998 - 财政年份:2003
- 资助金额:
$ 44.17万 - 项目类别:
Fi02 and Blood Vessel Formation in Adult Lung
Fi02 与成人肺中的血管形成
- 批准号:
7027038 - 财政年份:2003
- 资助金额:
$ 44.17万 - 项目类别:
ENDOTHELIUM AND VESSEL MATRIX IN PULMONARY HYPERTENSION
肺动脉高压中的内皮和血管基质
- 批准号:
2292126 - 财政年份:1995
- 资助金额:
$ 44.17万 - 项目类别:
ENDOTHELIUM AND VESSEL MATRIX IN PULMONARY HYPERTENSION
肺动脉高压中的内皮和血管基质
- 批准号:
2292127 - 财政年份:1995
- 资助金额:
$ 44.17万 - 项目类别:
相似海外基金
Combinatorial cytokine-coated macrophages for targeted immunomodulation in acute lung injury
组合细胞因子包被的巨噬细胞用于急性肺损伤的靶向免疫调节
- 批准号:
10648387 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Inducible HMGB1 antagonist for viral-induced acute lung injury.
诱导型 HMGB1 拮抗剂,用于治疗病毒引起的急性肺损伤。
- 批准号:
10591804 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
MAP2K1 AND MAP2K2 IN ACUTE LUNG INJURY AND RESOLUTION
MAP2K1 和 MAP2K2 在急性肺损伤中的作用及缓解
- 批准号:
10741574 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Lung epithelial cell-derived C3 in acute lung injury
肺上皮细胞衍生的 C3 在急性肺损伤中的作用
- 批准号:
10720687 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Examining the role of TRMT1 and tRNA methylation in acute lung injury and ARDS
检查 TRMT1 和 tRNA 甲基化在急性肺损伤和 ARDS 中的作用
- 批准号:
10719249 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Development of a new treatment for COVID-19-related acute lung injury targeting the microbiota-derived peptide corisin
针对微生物群衍生肽 corisin 开发治疗 COVID-19 相关急性肺损伤的新疗法
- 批准号:
23K07651 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Probing immunovascular mechanobiology in pneumonia-associated acute lung injury at the single capillary level
在单毛细血管水平探讨肺炎相关急性肺损伤的免疫血管力学生物学
- 批准号:
10679944 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
The amyloid precursor protein protects against acute lung injury
淀粉样前体蛋白可预防急性肺损伤
- 批准号:
10575258 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Role of macrophages and miRNA in regulating lung macrophage polarization and lung pathogenesis during respiratory virus-induced acute lung injury in normal and diabetic Syrian hamsters.
正常和糖尿病叙利亚仓鼠呼吸道病毒引起的急性肺损伤期间巨噬细胞和 miRNA 在调节肺巨噬细胞极化和肺部发病机制中的作用。
- 批准号:
10701207 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别:
Roles of N-glycans on neutrophil beta2 integrins in progression of acute lung injury
N-聚糖对中性粒细胞β2整合素在急性肺损伤进展中的作用
- 批准号:
10837431 - 财政年份:2023
- 资助金额:
$ 44.17万 - 项目类别: