Cell Recruitment Induced by ECM Scaffold Degradation

ECM 支架降解诱导的细胞募集

• 批准号: 7473251
• 负责人: Stephen F. Badylak
• 金额: $ 40.45万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-28 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7473251
• 关键词: Address; Affect; Antimicrobial Effect; Biology; Bone Marrow; Cell Communication; Cell Lineage; Cells; Chemicals; Chemotactic Factors; Cicatrix; Commit; Communities; Complex Mixtures; Dermal; Dermis; Distant; Event; Experimental Designs; Extracellular Matrix; Extracellular Matrix Degradation; Family; Fetal Development; Generations; Goals; Growth Factor; Harvest; Healed; Hepatic; Homeostasis; Homing; Human; In Vitro; Inflammation; Injury; Literature; Liver; Logic; Mechanics; Medical; Methods; Molecular; Molecular Weight; Organ; Parents; Peptides; Phenotype; Physicians; Placenta; Play; Population; Prevention; Principal Investigator; Process; Property; Purpose; Range; Recruitment Activity; Regenerative Medicine; Research Personnel; Role; Series; Signal Transduction; Site; Skin; Source; Specificity; Staging; Stem cells; Therapeutic; TimeLine; Tissue Engineering; Tissues; Work; Wound Healing; amnion; angiogenesis; base; cell type; clinical application; crosslink; cytokine; experience; fetal; healing; in vivo; injured; preclinical study; prevent; programs; reconstitution; reconstruction; repaired; response; scaffold; trafficking

DESCRIPTION (provided by applicant): The long term objective of our work is to optimize and more fully understand the methods by which the extracellular matrix (ECM) can be used as a biologic scaffold to promote the structural and functional reconstitution of injured or missing tissues and organs. The ECM provides structural support for tissues, serves as a storage depot for growth factors, and facilitates cell: cell communication. We propose to investigate a previously unrecognized function of the ECM; specifically, that it participates in the active recruitment of progenitor cells via the release of newly formed bioactive peptides derived from the degradation of intact ECM following tissue injury. Our preliminary studies show that chemical and enzymatic degradation of the extracellular matrix results in low molecular weight fractions (approximately 5-16 kDa) that possess diverse biologic activities including chemoattraction for progenitor cells from various tissues. We have-developed a working hypothesis that degradation products of the extracellular matrix of each tissue have tissue-specific chemoattractant properties for progenitor cells that are lineage committed for that particular tissue or organ. We propose a series of complementary studies that will address three Specific Aims. First, we will determine if degradation products of extracellular matrix harvested from either the dermis or the liver are chemoattractant for progenitor cells; both multipotential progenitor cells and lineage- committed (skin vs. liver) progenitor cells. Second, we will determine if prevention of ECM degradation in vivo affects (i.e., prevents) the participation of progenitor cells in the host remodeling response. Finally, we will isolate and purify chemoattractant peptides derived from hepatic and dermal ECM. This proposal is interdisciplinary in its approach and seeks to apply fundamental principles of biology and wound healing to the emerging field of regenerative medicine. The work will be conducted by an experienced team of tissue engineers, biochemists, stem cell biologists, molecular biologists, and physicians. The objectives of the studies, the hypothesis upon which the experimental design is based, and a timeline for completion of the studies are presented.

描述（由申请人提供）：我们工作的长期目标是优化和更充分理解细胞外基质（ECM）可以用作生物支架的方法，以促进受伤或缺失组织和器官的结构和功能重新建立。 ECM为组织提供结构支持，用作生长因子的存储库，并促进细胞：细胞通信。我们建议研究ECM先前未认识到的功能。具体而言，它通过释放组织损伤后完整的ECM降解而衍生出的新形成的生物活性肽来参与祖细胞的主动募集。我们的初步研究表明，细胞外基质的化学和酶促降解导致低分子量分数（约5-16 kDa）具有多种生物学活性，包括来自各种组织的祖细胞的化学疗法。我们已经开发了一个有效的假设，即每个组织的细胞外基质的降解产物具有组织特异性的化学吸收剂特性，用于用于该特定组织或器官的谱系谱系。我们提出了一系列互补研究，该研究将解决三个具体目标。首先，我们将确定从真皮或肝脏收获的细胞外基质的降解产物是否是祖细胞的化学吸引剂。多稳态的祖细胞和谱系（皮肤与肝脏）祖细胞。其次，我们将确定体内ECM降解的预防是否影响（即防止）祖细胞参与宿主重塑反应。最后，我们将隔离并纯化从肝和皮肤ECM衍生的趋化肽。该提议的方法是跨学科的，并试图将生物学的基本原理和伤口愈合应用于再生医学的新兴领域。这项工作将由经验丰富的组织工程师，生物化学家，干细​​胞生物学家，分子生物学家和医生进行。研究的目标，实验设计所基于的假设以及完成研究的时间表。