Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
基本信息
- 批准号:10471405
- 负责人:
- 金额:$ 59.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-01-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AtherosclerosisAutoimmune DiseasesBehaviorBiocompatible MaterialsBlood VesselsBrain IschemiaCell TherapyComplexCuesDataDiabetes MellitusDiseaseEndothelial CellsExhibitsExpression ProfilingFunctional disorderGene ExpressionGoalsGrowthHeartHindlimbHumanImpaired healingImpairmentIn VitroInflammatoryInflammatory ResponseInterleukin 4 ReceptorInterleukin-4IschemiaKineticsLeukocyte TraffickingMediatingMediator of activation proteinModelingMusMyocardial IschemiaPathologic NeovascularizationPathway interactionsPatientsPharmaceutical PreparationsPhasePhenotypePopulationProcessRegulationRegulatory T-LymphocyteSignal TransductionStimulusSupporting CellTestingTherapeuticTimeTissue EngineeringTissuesVascularizationWorkangiogenesiscancer therapycell motilitychronic wounddesigndirected differentiationefficacy testinghealingimmunoregulationimprovedin vitro testingin vivomacrophagemimicrymonocytemouse modelneovascularizationnovelnovel strategiesprotein expressionreceptorrecruitregeneration functionregenerativeresponseresponse to injurywound healing
项目摘要
Project Summary
At the heart of angiogenesis and biomaterial vascularization lies the inflammatory response, orchestrated
primarily by macrophages, which dramatically shift phenotype over time in response to microenvironmental cues.
In the normal response to injury, macrophages are initially pro-inflammatory (aka M1), and at later stages they
are replaced by a mixed population referred to collectively as M2 that upregulate factors associated with
resolution of the wound healing process. The extent of the diversity of this M2 population in particular is not
known. At later stages of angiogenesis and biomaterial vascularization, M2 macrophages are generated 1) via
transition from M1 macrophages, or 2) from direct differentiation of newly arriving monocytes. The differences
between the M2 macrophages arising from each population have not been investigated. Preliminary data
suggest that M1-derived M2 macrophages possess enhanced angiogenic functionality, and that biomaterials
that transiently stimulate the initial M1 phase may enhance the subsequent response to M2-promoting
biomaterials to achieve enhanced vascularization and healing. The overarching hypothesis of this project is that
biomaterials that promote sequential M1 and M2 activation of the same population of macrophages will enhance
vascularization. To test this hypothesis, this work has the following goals: 1) Determine the effects of M1 pre-
polarization on the functional phenotype of M2 macrophages in crosstalk with blood vessels in vitro, using
primary human macrophages, gene and protein expression profiling, and tissue-engineered models of
angiogenesis. 2) Determine the effects of pro-inflammatory pre-treatment on the regenerative effects of IL4-
releasing biomaterials in vivo, using biomaterials that temporally control the phenotype of host macrophages in
a murine hindlimb ischemia model. 3) Determine the angiogenic effects in vivo of a biomaterial-mediated
macrophage cell therapy strategy that intracellularly directs a single population of macrophages from M1 to M2.
This latter strategy may result in particularly beneficial biomaterials for patients who suffer from impaired
leukocyte trafficking, including patients with diabetes, autoimmune disease, or those undergoing
chemotherapeutic treatment for cancer. This work will advance our understanding of how biomaterials can be
designed to leverage both the inflammatory and regenerative functions of macrophages to enhance
angiogenesis, which will allow us to develop new strategies to treat numerous diseases characterized by
pathological angiogenesis, including heart and brain ischemia, atherosclerosis, and diabetes, among many
others. In addition, this project proposes a novel approach to direct tissue revascularization by controlling the
actions of both recruited and exogenously administered macrophages using biomaterials.
项目概要
血管生成和生物材料血管化的核心在于精心策划的炎症反应
主要是通过巨噬细胞,随着时间的推移,巨噬细胞会根据微环境线索显着改变表型。
在对损伤的正常反应中,巨噬细胞最初是促炎细胞(又名 M1),在后期阶段,它们
被统称为 M2 的混合群体所取代,M2 上调与
解决伤口愈合过程。 M2 群体的多样性程度尤其不
已知。在血管生成和生物材料血管化的后期阶段,M2 巨噬细胞通过 1) 生成:
从 M1 巨噬细胞转变,或 2) 从新到达的单核细胞直接分化。差异
尚未研究每个群体产生的 M2 巨噬细胞之间的差异。初步数据
表明 M1 衍生的 M2 巨噬细胞具有增强的血管生成功能,并且生物材料
短暂刺激初始 M1 阶段可能会增强对 M2 促进的后续反应
生物材料以实现增强的血管化和愈合。该项目的总体假设是
促进同一巨噬细胞群的 M1 和 M2 连续激活的生物材料将增强
血管化。为了检验这个假设,这项工作有以下目标:1)确定 M1 预置的效果
体外与血管串扰时 M2 巨噬细胞功能表型的极化,使用
原代人类巨噬细胞、基因和蛋白质表达谱以及组织工程模型
血管生成。 2) 确定促炎预处理对IL4-再生作用的影响
使用暂时控制宿主巨噬细胞表型的生物材料在体内释放生物材料
小鼠后肢缺血模型。 3) 确定生物材料介导的体内血管生成作用
巨噬细胞治疗策略,在细胞内将单个巨噬细胞群从 M1 引导至 M2。
后一种策略可能会为患有功能障碍的患者带来特别有益的生物材料。
白细胞贩运,包括患有糖尿病、自身免疫性疾病或正在接受治疗的患者
癌症的化疗。这项工作将增进我们对生物材料如何应用的理解
旨在利用巨噬细胞的炎症和再生功能来增强
血管生成,这将使我们能够开发新的策略来治疗以
病理性血管生成,包括心脏和大脑缺血、动脉粥样硬化和糖尿病等
其他的。此外,该项目提出了一种通过控制直接组织血运重建的新方法
使用生物材料招募和外源施用的巨噬细胞的作用。
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)
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Kara Lorraine Spiller其他文献
Kara Lorraine Spiller的其他文献
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{{ truncateString('Kara Lorraine Spiller', 18)}}的其他基金
Particle-Assisted Control over Macrophage-Neutrophil interactions (Pac-Man)
巨噬细胞-中性粒细胞相互作用的粒子辅助控制(吃豆人)
- 批准号:
10725989 - 财政年份:2023
- 资助金额:
$ 59.53万 - 项目类别:
Inflammation-related gene biomarkers in human diabetic foot ulcer healing
人类糖尿病足溃疡愈合中的炎症相关基因生物标志物
- 批准号:
10658986 - 财政年份:2022
- 资助金额:
$ 59.53万 - 项目类别:
Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
- 批准号:
9340738 - 财政年份:2017
- 资助金额:
$ 59.53万 - 项目类别:
Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
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10296177 - 财政年份:2016
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$ 59.53万 - 项目类别:
Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
- 批准号:
9198940 - 财政年份:2016
- 资助金额:
$ 59.53万 - 项目类别:
Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
- 批准号:
10629777 - 财政年份:2016
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$ 59.53万 - 项目类别:
Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
- 批准号:
10889772 - 财政年份:2016
- 资助金额:
$ 59.53万 - 项目类别:
Understanding and Controlling Macrophage Behavior in Angiogenesis
了解和控制血管生成中的巨噬细胞行为
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