BIOLOGY OF TISSUE ENGINEERED ENDOTHELIAL IMPLANTS

组织工程内皮植入物的生物学

• 批准号: 6389930
• 负责人: Elazer R Edelman
• 金额: $ 39.17万
• 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/6389930
• 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.

这项资助一方面利用组织工程学来检查内皮细胞生理学，另一方面又利用组织工程来研究心血管疾病的基础。这两者是相互关联的。完整的内皮调节血管生物学的方方面面，确保血管静止，调节血管修复。许多心血管疾病似乎始于血管内皮细胞防御机制的破坏并通过其传播。然而，目前尚不清楚内皮控制是源于管腔边界的内皮细胞的物理存在，还是源于完整的内皮细胞分泌的化合物。这个问题的答案可能会决定我们如何理解、诊断、设计新的治疗方法和治疗各种血管疾病。这一建议旨在更好地了解内皮细胞在调节血管增生性疾病中的生化作用，而不是由管腔界面上的内皮建立的物理屏障力量所建立的。我们在组织工程化内皮细胞移植方面的工作有助于加深对这一领域的了解。内皮细胞被嵌入在海绵状的聚合物材料中，其三维结构确保了大量的细胞可以被放置在邻近靶组织的保护性支架中。我们已经表征了嵌入细胞的细胞分泌活性，并证明了它们在聚合物设备中保留了内皮生长特征、免疫特性和生存能力。当植入受损动脉周围时，预期的增殖性病变会显着减少。这些嫁接使我们能够将结构与功能分离，特别是将通过一系列实验来探索两组目标。这些目的包括：1.确定在高等物种动物模型中，血管对深度损伤反应的哪个阶段受内皮细胞移植物的调节。2.阐明体内植入内皮细胞调控血管修复的生化合成功能。这个项目是我们将许多不同学科结合在一起来解决这些问题的第一次机会。我们希望，所吸取的经验教训将被用于最广泛的基础细胞和分子生物学的疾病血管病理生理学，并继续创造和应用创新的分子、细胞和药物治疗心血管疾病的方法。