Cardiac Remodeling with Organ Specific Extracellular Matrix Scaffolds

使用器官特异性细胞外基质支架进行心脏重塑

• 批准号: 7841900
• 负责人: Thomas W. Gilbert
• 金额: $ 7.19万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7841900
• 关键词: 5 year old; Adult; Affect; American; Architecture; Area; Behavior; Biological; Biomechanics; Bladder; Bone Marrow; Bone Marrow Cells; Caliber; Canis familiaris; Cardiac; Cardiac Myocytes; Cardiac Surgery procedures; Cattle; Cell Therapy; Cells; Characteristics; Chemotactic Factors; Childhood; Confocal Microscopy; Congenital Abnormality; Congenital Heart Defects; Defect; Dermis; Development; Devices; Diagnosis; Disease Progression; Endothelial Cells; Equipment Malfunction; Extracellular Matrix; Family suidae; Fluorescence-Activated Cell Sorting; Fluorescent in Situ Hybridization; Goals; Green Fluorescent Proteins; Heart; Heart Transplantation; Heart failure; Human; Individual; Location; Marrow; Measurement; Mechanics; Modality; Modeling; Morphology; Myocardial; Myocardial tissue; Myocardium; Operative Surgical Procedures; Organ; Organ Donor; Pathologist; Patients; Penetration; Phenotype; Physicians; Physiological; Play; Population; Procedures; Process; Proliferating; Property; Proto-Oncogene Protein c-kit; Rattus; Recruitment Activity; Regenerative Medicine; Repeat Surgery; Right ventricular structure; Role; Sepsis; Signal Transduction; Site; Small Intestinal Submucosa; Source; Stem cells; Structure; Tetralogy of Fallot; Thick; TimeLine; Tissue Engineering; Tissues; Ventricular; Woman; base; biomechanical engineering; body system; cell motility; dacron; experience; fetal; improved; men; mortality; operation; pressure; progenitor; public health relevance; reconstruction; repaired; response; restoration; scaffold; sex; success; tissue reconstruction

DESCRIPTION (provided by applicant): Improved materials for cardiac reconstruction of congenital defects and heart failure are needed. Current surgical approaches for cardiac reconstruction utilize synthetic materials that slow the progression of disease, but do not provide any contractile function and do not have the ability to grow with the patient. Recently, porcine urinary bladder matrix (UBM) has been used to repair myocardial tissue. The remodeled UBM contributed to regional function in both canine and porcine models, but did not fully restore myocardial tissue. Cardiac extracellular matrix (C-ECM) may promote faster reconstruction of functional tissue by providing a scaffold with a composition and architecture similar to the tissue that it be intended to replace. The proposed study will determine the morphologic and functional differences in cardiac remodeling after repair with C-ECM, UBM, and Dacron patches. Furthermore, the study will include analysis of the recruitment and fate of bone marrow derived progenitor cells at the site of remodeling. An experienced interdisciplinary team consisting of biomechanical engineers, tissue engineers, physicians, and pathologists has been assembled to conduct these studies. A timeline for completion of these studies and quantitative criteria for success are provided. PUBLIC HEALTH RELEVANCE: Regenerative medicine approaches, such as naturally occurring extracellular matrix (ECM) scaffolds offer potential alternatives to surgical repair for congenital cardiac defects and adult heart failure. The current proposal will investigate efficacy of an ECM scaffolds derived from porcine myocardium for repair of a cardiac defect. The goal of the proposal is to determine if organ specific ECM is preferable for cardiac repair and whether bone marrow progenitor cells participate in the remodeling process.

描述（由申请人提供）：需要改进的先天性缺陷和心力衰竭的心脏重建材料。当前的心脏重建手术方法利用降低疾病进展但不提供任何收缩功能的合成材料，并且没有能力与患者一起成长。最近，猪泌尿膀胱基质（UBM）已用于修复心肌组织。改建后的UBM在犬和猪模型中都促进了区域功能，但没有完全恢复心肌组织。心脏外基质（C-ECM）可以通过提供与旨在更换的组织相似的组成和结构的支架来促进功能组织的更快重建。拟议的研究将确定用C-ECM，UBM和DACRON斑块修复后心脏重塑的形态和功能差异。此外，该研究将包括对重塑部位骨髓衍生的祖细胞的募集和命运的分析。一支由生物力学工程师，组织工程师，医师和病理学家组成的经验丰富的跨学科团队已组成，以进行这些研究。提供了完成这些研究的时间表和成功的定量标准。公共卫生相关性：再生医学方法，例如天然存在的细胞外基质（ECM）脚手架，为先天性心脏缺陷和成人心力衰竭提供了手术修复的潜在替代方法。当前的建议将研究源自猪心肌的ECM支架的功效，以修复心脏缺陷。该提案的目的是确定器官特异性ECM是否优于心脏修复以及骨髓祖细胞是否参与重塑过程。