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:
    10629777
  • 负责人:
  • 金额:
    $ 7.74万
  • 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

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. Previously we showed that M1 macrophages are critical for the initiation of angiogenesis, but they must switch to M2 for stable angiogenesis and wound healing. The extent of the diversity of this M2 population, and how they regulate angiogenic processes, is still unknown. 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. We recently found that adoptively transferred macrophages and M2-promoting microparticles are synergistic in promoting tissue revascularization in a murine hindlimb ischemia model. However, the macrophages were rapidly cleared from the site of injury (within 2 days), making it difficult to study the phenotype changes in adoptively transferred macrophages. Therefore, the goal of this project is to adoptively transfer macrophages using biomaterial scaffolds as a cell carrier, so that the macrophages are retained at the site of injury for long enough to track their phenotype changes and to observe their interactions with other cell types involved in angiogenesis. We will use porous scaffolds (as opposed to hydrogels) because other work in our lab has shown using in vitro studies that macrophage-T cell crosstalk is important for the M1-to-M2 transition of macrophages, so it is important that T cells are able to inflitrate the biomaterial carrier. In the current project, we will administer pro-inflammatory M1 macrophages to the site of injury using porous scaffolds in order to test the hypothesis that M1 macrophage crosstalk with T cells promotes Th2 differentiation in T cells, the M1-to-M2 transition in macrophages, and enhanced angiogenesis. The hypothesis is that adoptively transferred M1 macrophages will transition into a distinct M2 phenotype with enhanced angiogenic functions (compared to M0 macrophages) via crosstalk with endogenous T cells.
项目摘要 血管生成和生物材料血管化的核心是炎症反应, 主要是巨噬细胞,其响应于微环境线索而随着时间的推移显著改变表型。 在对损伤的正常反应中,巨噬细胞最初是促炎性的(又名M1),在后期阶段, 被统称为M2的混合群体所取代,其上调与以下相关的因子: 解决伤口愈合过程。以前我们表明,M1巨噬细胞是关键的启动 但它们必须转换为M2以稳定血管生成和伤口愈合。的程度 该M2群体的多样性以及它们如何调节血管生成过程仍然未知。在后期阶段, 血管生成和生物材料血管化,M2巨噬细胞1)通过从M1 巨噬细胞,或2)来自新到达的单核细胞的直接分化。M2的区别 还没有研究从每种群体产生的巨噬细胞。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, 初始M1期可以增强随后对M2促进生物材料的反应,以实现增强的 血管化和愈合。这个项目的首要假设是,生物材料,促进 相同巨噬细胞群的顺序M1和M2活化将增强血管形成。 我们最近发现,过继转移的巨噬细胞和M2促进微粒, 在促进鼠后肢缺血模型中的组织再血管化方面具有协同作用。但 巨噬细胞从损伤部位迅速清除(2天内),使得难以研究表型 过继转移巨噬细胞的变化。因此,本项目的目标是采用 使用生物材料支架作为细胞载体的巨噬细胞,使得巨噬细胞保留在植入部位。 损伤足够长的时间来跟踪它们的表型变化并观察它们与其他细胞类型的相互作用 参与血管生成。我们将使用多孔支架(而不是水凝胶),因为我们实验室的其他工作 已经使用体外研究表明,巨噬细胞-T细胞串扰对于M1到M2的转变是重要的, 因此,T细胞能够浸润生物材料载体是重要的。在目前的项目中,我们 将使用多孔支架将促炎性M1巨噬细胞给予损伤部位,以测试 假设M1巨噬细胞与T细胞的相互作用促进T细胞中的Th 2分化,M1到M2 在巨噬细胞中的转化和增强的血管生成。 假设过继转移的M1巨噬细胞将转变为不同的M2巨噬细胞, 表型与增强的血管生成功能(与M0巨噬细胞相比)通过串扰与 内源性T细胞

项目成果

期刊论文数量(0)
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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:
    $ 7.74万
  • 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:
    $ 7.74万
  • 项目类别:
Immune Modulation & Engineering Symposium
免疫调节
  • 批准号:
    10392105
  • 财政年份:
    2020
  • 资助金额:
    $ 7.74万
  • 项目类别:
Immune Modulation & Engineering Symposium
免疫调节
  • 批准号:
    10609295
  • 财政年份:
    2020
  • 资助金额:
    $ 7.74万
  • 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:
    $ 7.74万
  • 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:
    9002582
  • 财政年份:
    2016
  • 资助金额:
    $ 7.74万
  • 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:
    $ 7.74万
  • 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:
    $ 7.74万
  • 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:
    10296177
  • 财政年份:
    2016
  • 资助金额:
    $ 7.74万
  • 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:
    10682565
  • 财政年份:
    2016
  • 资助金额:
    $ 7.74万
  • 项目类别:

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