BIOLOGY OF TISSUE ENGINEERED ENDOTHELIAL IMPLANTS

组织工程内皮植入物的生物学

• 批准号: 6184490
• 负责人: Elazer R Edelman
• 金额: $ 38.03万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-28 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184490
• 关键词: angiogenesis; biomaterial interface interaction; cardiovascular disorder; cell biology; cell growth regulation; cell proliferation; homeostasis; implant; polymers; swine; tissue /cell culture; tissue engineering; tissue support frame; vascular endothelium

This grant utilizes tissue engineering to examine endothelial cell physiology on one hand and the basis of cardiovascular diseases on the other. The two are interrelated. The intact endothelium regulates all aspects of vascular biology, insures vascular quiescence and regulates vascular repair. Many cardiovascular diseases appear to begin with and propagate through disruption of the endothelial defense mechanisms. Yet, it is not clear whether endothelial control arises from the physical presence of the endothelium at the lumenal border or from the compounds intact endothelial cells secrete. The answer to this question may dictate how we understand, diagnose, design new therapies for and treat the full gamut of vascular disease. This proposal seeks to understand better the biochemical role of the endothelial cell in regulating vasoproliferative diseases, above and beyond that established by the physical barrier forces established by the endothelium at the luminal interface. Our work with tissue-engineered endothelial cell implants has helped to add to understanding in this area. Endothelial cells are embedded within sponge-like polymeric materials whose three dimensional configuration insures that large number of cells can be placed in a protective scaffolding adjacent to target tissues. We have characterized the cell secretory activity of embedded cells, and have demonstrated their retention of endothelial growth characteristics, immune identity and viability within the polymeric devices. When implanted around injured arteries the expected proliferative lesions are dramatically reduced. These grafts allow us to divorce structure from function and in particular will enable exploration of two groups of aims with a series of experiments. These aims include: 1. Determination of which of the phases of the vascular response to deep injury in higher species animal models are regulated by endothelial cell grafts. 2. elucidation of the biochemical synthetic functions that underlie engrafted endothelial cell control of vascular repair in vivo. This program is the first opportunity we will have to bring many diverse disciplines together to address these issues. We hope that the lessons learned will be utilized in the broadest context of fundamental cell and molecular biology of the vascular pathophysiology of disease, and for the continued creation and application of innovative molecular, cellular and pharmacological therapies for cardiovascular disease.

该赠款一方面利用组织工程检查内皮细胞生理，另一方面是心血管疾病的基础。两者相互关联。完整的内皮调节血管生物学的各个方面，确保血管静止并调节血管修复。许多心血管疾病似乎是从内皮防御机制的破坏开始并传播的。然而，尚不清楚内皮控制是由内皮在腔内边界的物理存在还是由化合物完整的内皮细胞分泌。 这个问题的答案可能决定了我们如何理解，诊断，设计新疗法并治疗全部血管疾病。该提案旨在更好地理解内皮细胞在调节血管增生性疾病中的生化作用，而不是由内皮在腔内界面上建立的物理屏障力所确定的，而不是在腔界面上确定的生化作用。我们在组织设计的内皮细胞植入物中的工作有助于增加该领域的理解。内皮细胞嵌入海绵样聚合物材料中，其三维构型确保可以将大量细胞置于靶组织附近的保护性脚手架中。 我们已经表征了嵌入式细胞的细胞分泌活性，并证明了它们在聚合物装置内的内皮生长特征，免疫认同和生存力的保留。当在受伤的动脉周围植入时，预期的增殖病变会大大减少。这些移植物使我们能够通过功能与结构离婚，特别是可以通过一系列实验来探索两组目标。这些目的包括：1。确定较高物种模型的血管对深损伤的阶段的确定受内皮细胞移植的调节。 2。阐明生化合成功能是植入体内血管修复的内皮细胞控制的基础。该计划是我们将不得不将许多多样化学科聚集在一起以解决这些问题的第一个机会。我们希望所学的经验教训能够在疾病血管病理生理学的基本细胞和分子生物学的最广泛背景下使用，并继续创建和应用创新的分子，细胞和药理学治疗心血管疾病。