Cellular Remodeling of ECM Scaffolds

ECM 支架的细胞重塑

• 批准号: 7392772
• 负责人: Stephen F. Badylak
• 金额: $ 31.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7392772
• 关键词: Address; Angiogenic Peptides; Animals; Antigen Presentation; Binding; Biology; Blood Vessels; Bone Marrow; Bone Marrow Cells; Bone Marrow Involvement; Cardiovascular system; Cell Lineage; Cell-Matrix Junction; Cells; Cellular biology; Chemicals; Chemotactic Factors; Cicatrix; Clinical; Collagen; Complement; Deposition; Development; Dura Mater; End Point; Esophagus; Extracellular Matrix; Extracellular Matrix Degradation; Fibroblast Growth Factor; Fibroblasts; Growth Factor; Hematopoietic; Hematopoietic stem cells; Heparitin Sulfate; Human; Inflammatory Response; Laboratories; Laminin; Ligands; Localized; Location; Lower urinary tract; Marrow; Mediating; Medicine; Modeling; Natural regeneration; Numbers; Operative Surgical Procedures; Pattern; Peptides; Placement; Play; Population; Principal Investigator; Process; Property; Recruitment Activity; Regenerative Medicine; Relative (related person); Research Personnel; Rodent Model; Role; Signal Transduction; Site; Skin; Source; Stem Cell Development; Stem cells; Structure; Subcutaneous Tissue; Testing; Thick; Time; TimeLine; Tissue Engineering; Tissues; Transgenic Organisms; Vascular Endothelial Cell; Work; Wound Healing; achilles tendon; angiogenesis; base; cell motility; clinical application; crosslink; day; implantation; in vivo; injured; migration; mouse model; neovascularization; pre-clinical; precursor cell; programs; reconstruction; repaired; scaffold; self assembly; soft tissue; transdifferentiation

DESCRIPTION (provided by applicant): Biologic scaffolds composed of extracellular matrix (ECM) have been successfully used as inductive templates for the constructive remodeling of many tissues including the lower urinary tract, skin, musculotendinous tissues and esophagus, among others in both preclinical animal studies and in human clinical applications. However, the mechanisms by which this constructive remodeling process occurs in diverse tissues is largely unknown. The source of cells that populate and participate in the ECM remodeling process is a source of controversy and the ability to control such a cell population would represent a significant technical advance in the field of regenerative medicine. The proposed work will address a very focused aspect of the cellular remodeling process. Specifically, we will examine the temporal and spatial patterns of ECM remodeling by two populations of cells: ciculating fibrocytes and local tissue fibroblasts. Circulating fibrocytes are a population of marrow derived cells of hematopoietic origin that have been shown to participate in wound healing, angiogenesis, antigen presentation, and tissue remodeling. To date, these cells have not been examined for their role in tissue reconstruction with an ECM based scaffold approach. We will examine both the bone marrow and surrounding soft tissue as potential sources of both circulating fibrocytes and local tissue fibroblasts during the remodeling process. Using chimeric and transgenic mouse models we will track selected cell populations during studies to accomplish two specific aims. The first specific aim will determine the involvement of bone marrow derived fibrocytes in the remodeling process of ECM biologic scaffolds. The second specific aim will determine the role of local tissue fibroblasts in the remodeling process. We have assembled a highly interdisciplinary team with expertise in medicine, surgery, tissue engineering, ECM biology, stem cell biology, and cellular differentiation. We have identified clearly defined specific aims with quantifiable end points and an efficient three year timeline to conduct this work.

描述（由申请人提供）：由细胞外基质（ECM）组成的生物支架已成功用作电感模板，用于对许多组织的建设性重塑，包括下尿路，皮肤，肌肉座性组织和肌肉座性组织和食管，以及在人类临床临床上的其他组织。但是，这种建设性重塑过程在不同组织中发生的机制在很大程度上是未知的。填充和参与ECM重塑过程的细胞来源是争议的根源，控制这种细胞群体的能力将代表再生医学领域的重大技术进步。拟议的工作将解决细胞重塑过程中非常重点的方面。具体而言，我们将检查两个细胞种群进行ECM重塑的时间和空间模式：固定纤维细胞和局部组织成纤维细胞。循环纤维细胞是造血起源的骨髓衍生细胞群，已显示出参与伤口愈合，血管生成，抗原表现和组织重塑。迄今为止，尚未使用基于ECM的支架方法来检查这些细胞在组织重建中的作用。我们将研究骨髓和周围软组织，作为在重塑过程中循环纤维细胞和局部组织成纤维细胞的潜在来源。使用嵌合和转基因小鼠模型，我们将在研究过程中跟踪选定的细胞群，以实现两个具体的目标。第一个具体目的将确定骨髓衍生的纤维细胞参与ECM生物支架的重塑过程。第二个特定目的将决定局部组织成纤维细胞在重塑过程中的作用。我们已经组建了一个高度的跨学科团队，具有医学，手术，组织工程，ECM生物学，干细胞生物学和细胞分化方面的专业知识。我们已经确定了具有可量化终点的明确定义的特定目标，并有一个有效的三年时间表来进行这项工作。