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
• 负责人: Vineet Agrawal
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8122283
• 关键词: Adult; Anti-Inflammatory Agents; Anti-inflammatory; Chemotaxis; Cicatrix; Complex; Extracellular Matrix; Extracellular Matrix Degradation; Family suidae; Foundations; Future; Goals; Human; Immune system; In Vitro; Inflammation Process; Injury; Investigation; Mammals; Mediating; Methods; Modeling; Molecular; Multipotent Stem Cells; Mus; Muscle; Natural regeneration; Patients; Peptides; Phenotype; Play; Process; Public Health; Recovery of Function; Recruitment Activity; Relative (related person); Risk; Role; Site; Stem cells; Tissues; cell motility; crosslink; implantation; in vivo; macrophage; mouse model; repaired; research study; response to injury; scaffold; soft tissue; stem cell population; stem cell therapy; tissue regeneration; tumorigenesis; wound

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.

描述（由申请人提供）： 成年哺乳动物对损伤的再生仅限于选定的组织。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。伤口的微环境在决定成年哺乳动物的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，被招募到伤口微环境的干细胞促进了一种称为外胚再生的过程。由猪源细胞外基质 (ECM) 组成的生物支架已成功用于超过一百万人类患者，以创造伤口微环境，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 支架会导致快速降解、生物活性肽释放、局部巨噬细胞极化和内源干细胞招募。 ECM介导的体内干细胞募集的机制尚不清楚，但可能部分是由ECM降解后释放的分子介导的。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招募中的作用，（2）ECM 降解对体外和体内巨噬细胞极化的作用，以及（3） ECM降解和极化巨噬细胞对体内内源干细胞募集的相对贡献。本研究的结果进一步让我们了解先天免疫系统在促进组织再生中的作用，并将为进一步研究细胞外基质成分与先天免疫系统之间相互作用的机制奠定基础。和内源性干细胞。