ECM Degradation and Macrophage Polarization in Endogenous Stem Cell Recruitment

内源干细胞招募中的 ECM 降解和巨噬细胞极化

基本信息

  • 批准号:
    7912172
  • 负责人:
  • 金额:
    $ 4.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-07-06 至 2014-07-05
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Regeneration in response to injury is limited to select tissues in adult mammals. The default response to injury in most other tissues involves the processes of inflammation and scar tissue formation (i.e., repair). The microenvironment of the wound plays an important role in determining regeneration versus scar in adult mammals. In species capable of regenerating complex tissues, stem cells recruited to the wound microenvironment promote a process known as epimorphic regeneration. Biologic scaffolds composed of porcine derived extracellular matrix (ECM) have successfully been used in over one million human patients to create a wound microenvironment that promotes site-specific, non-inflammatory repair of a variety of soft tissues. Implantation of an ECM scaffold following tissue injury results in rapid degradation, release of bioactive peptides, local macrophage polarization, and endogenous stem cell recruitment. The mechanisms underlying ECM mediated stem cell recruitment in vivo are well not understood, but may partially be mediated by molecules released following ECM degradation. Polarized macrophages are also capable of recruiting stem cells in vitro, but their contribution to endogenous stem cell recruitment in vivo is not well understood. The overall goal of the present study is to investigate: (1) role of ECM degradation in stem cell recruitment in vitro and in vivo, (2) the role of ECM degradation on macrophage polarization in vitro and in vivo, and (3) the relative contributions of ECM degradation and polarized macrophages upon endogenous stem cell recruitment in vivo. The findings of the present study further inform us on the on the role of the innate immune system in promoting tissue regeneration, and it will serve as the foundation of future studies to further investigate the mechanisms underlying interaction between extracellular matrix components, the innate immune system, and endogenous stem cells. PUBLIC HEALTH RELEVANCE: THE RELATION OF OUR STUDIES TO PUBLIC HEALTH: The findings from these studies will further our understanding of the respective contributions of the innate immune system and ECM scaffold degradation in promoting functional tissue regeneration. It will serve as the foundation of future avenues of investigation that will aim to develop more targeted therapies for promoting tissue regeneration and functional recovery following injury in humans.
描述(由申请人提供):损伤后的再生仅限于成年哺乳动物的特定组织。大多数其他组织对损伤的默认反应涉及炎症和疤痕组织形成(即修复)的过程。在成年哺乳动物中,伤口的微环境在决定再生与疤痕方面起着重要作用。在能够再生复杂组织的物种中,干细胞被招募到伤口微环境中,促进了一个被称为表形再生的过程。由猪源性细胞外基质(ECM)组成的生物支架已经成功地用于超过一百万的人类患者,以创造一个伤口微环境,促进各种软组织的部位特异性,非炎症修复。组织损伤后植入ECM支架可导致快速降解、释放生物活性肽、局部巨噬细胞极化和内源性干细胞募集。ECM介导的干细胞在体内募集的机制尚不清楚,但可能部分由ECM降解后释放的分子介导。极化巨噬细胞也能够在体外募集干细胞,但它们对体内内源性干细胞募集的贡献尚不清楚。本研究的总体目标是研究:(1)ECM降解在体外和体内干细胞募集中的作用,(2)ECM降解在体外和体内巨噬细胞极化中的作用,以及(3)ECM降解和极化巨噬细胞在体内内源性干细胞募集中的相对贡献。本研究结果进一步揭示了先天免疫系统在促进组织再生中的作用,为进一步研究细胞外基质成分、先天免疫系统和内源性干细胞之间相互作用的机制奠定了基础。

项目成果

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Vineet Agrawal其他文献

Vineet Agrawal的其他文献

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{{ truncateString('Vineet Agrawal', 18)}}的其他基金

A Pathogenic Role for the Natriuretic Peptide Clearance Receptor in Heart Failure with Preserved Ejection Fraction.
钠尿肽清除受体在射血分数保留的心力衰竭中的致病作用。
  • 批准号:
    10589324
  • 财政年份:
    2023
  • 资助金额:
    $ 4.64万
  • 项目类别:
A Pathogenic Role for Natriuretic Peptide Receptor-C in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction
钠尿肽受体-C 在肺动脉高压和射血分数保留的心力衰竭中的致病作用
  • 批准号:
    10463813
  • 财政年份:
    2021
  • 资助金额:
    $ 4.64万
  • 项目类别:
A Pathogenic Role for Natriuretic Peptide Receptor-C in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction
钠尿肽受体-C 在肺动脉高压和射血分数保留的心力衰竭中的致病作用
  • 批准号:
    10301687
  • 财政年份:
    2021
  • 资助金额:
    $ 4.64万
  • 项目类别:
ECM Degradation and Macrophage Polarization in Endogenous Stem Cell Recruitment
内源干细胞招募中的 ECM 降解和巨噬细胞极化
  • 批准号:
    8296675
  • 财政年份:
    2010
  • 资助金额:
    $ 4.64万
  • 项目类别:
ECM Degradation and Macrophage Polarization in Endogenous Stem Cell Recruitment
内源干细胞招募中的 ECM 降解和巨噬细胞极化
  • 批准号:
    8122283
  • 财政年份:
    2010
  • 资助金额:
    $ 4.64万
  • 项目类别:
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