3D Angiogenesis Assay for Heart Study

用于心脏研究的 3D 血管生成测定

• 批准号: 7746745
• 负责人: Timothy M. Ragan
• 金额: $ 16.56万
• 依托单位: TISSUEVISION, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-10 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7746745
• 关键词: Animal Model; Animals; Automation; Back; Biochemical; Biological Assay; Biological Models; Biomedical Engineering; Blood Vessels; Blood capillaries; Cardiac; Cause of Death; Cell Nucleus; Clinical Trials; Collaborations; Collagen; Complex; Computer software; Detection; Development; Discipline; Disease; Fibroblast Growth Factor; Fibroblast Growth Factor 2; Growth Factor; Heart; Heart Diseases; Hypoxia; Image; Image Analysis; In Situ; In Vitro; Individual; Infarction; Ischemia; Label; Malignant Neoplasms; Marketing; Microscopic; Microscopy; Microtome - medical device; Modeling; Morphology; Myocardial Infarction; Myocardial Ischemia; Myocardial tissue; Myocardium; Nature; Organ; Pharmacologic Substance; Physiological; Physiology; Play; Preparation; Process; Protocols documentation; Research Design; Research Personnel; Resolution; Retrieval; Role; Screening procedure; Series; Speed; Staging; Testing; Therapeutic; Three-Dimensional Image; Tissues; United States; Validation; Work; angiogenesis; base; capillary; cost; design and construction; drug candidate; drug development; in vivo; innovation; new growth; novel; programs; public health relevance; repaired; response; therapeutic angiogenesis; tool; Animal Model; Animals; Automation; Back; Biochemical; Biological Assay; Biological Models; Biomedical Engineering; Blood Vessels; Blood capillaries; Cardiac; Cause of Death; Cell Nucleus; Clinical Trials; Collaborations; Collagen; Complex; Computer software; Detection; Development; Discipline; Disease; Fibroblast Growth Factor; Fibroblast Growth Factor 2; Growth Factor; Heart; Heart Diseases; Hypoxia; Image; Image Analysis; In Situ; In Vitro; Individual; Infarction; Ischemia; Label; Malignant Neoplasms; Marketing; Microscopic; Microscopy; Microtome - medical device; Modeling; Morphology; Myocardial Infarction; Myocardial Ischemia; Myocardial tissue; Myocardium; Nature; Organ; Pharmacologic Substance; Physiological; Physiology; Play; Preparation; Process; Protocols documentation; Research Design; Research Personnel; Resolution; Retrieval; Role; Screening procedure; Series; Speed; Staging; Testing; Therapeutic; Three-Dimensional Image; Tissues; United States; Validation; Work; angiogenesis; base; capillary; cost; design and construction; drug candidate; drug development; in vivo; innovation; new growth; novel; programs; public health relevance; repaired; response; therapeutic angiogenesis; tool

DESCRIPTION (provided by applicant): Angiogenesis is the growth of new blood vessels from the existing vasculature. It is implicated in many diseases and disciplines, including heart disease where it plays an important role in repair of ischemic tissue following myocardial infarction. Heart disease is the second leading cause of death in the United States. Hope for effective angiogenesis therapies in ischemic heart disease has been dampened by a series of mostly disappointing clinical trials. Despite the importance of angiogenesis, there is a lack of effective angiogenesis assays and this is hampering progress in developing angiogenic therapeutics. While there exist a number of vitro and in vivo screening assays which can provide information about specific, narrow aspects of angiogenesis, it is often very difficult to interpret how the results of these assays pertain to the physiological relevant 3D microscopic tissue level where angiogenesis actually manifests. In particular, there is a conspicuous lack of assays that provide direct information about capillary morphology and function in situ even though this is ultimately the most important aspect of angiogenesis. This proposal is for the development of a high throughput 3D angiogenesis assay at the in situ tissue level. It accomplishes this by employing high speed 3D microscopic imaging, multispectral detection, advanced tissue labeling protocols, and software for high content image analysis. As a first application we will apply this to study the angiogenic response to fibroblast growth factor (bFGF) in myocardial ischemia. We believe this assay will become a valuable tool for basic researchers and provide crucial information in the late drug development process to pharmaceutical companies on whether to continue the development of a drug candidate. PUBLIC HEALTH RELEVANCE: This proposal describes the development of a new angiogenesis assay which we apply to the study of heart disease. Its key innovations are highly detailed 3D images of the microvascular, and the ability to this back to tissue physiology, composition and biochemical state. It has the strong potential to reduce the cost of doing angiogenesis assays in animal models as well as offer high physiological relevance and advance the use of angiogenesis therapies for the treatment of heart disease.

描述（由申请人提供）：血管生成是现有脉管系统的新血管的生长。它与许多疾病和学科有关，包括心脏病，在心肌梗塞后，它在修复缺血组织中起重要作用。心脏病是美国第二大死亡原因。一系列令人失望的临床试验使缺血性心脏病中有效的血管生成疗法受到希望。尽管血管生成很重要，但缺乏有效的血管生成测定法，这阻碍了开发血管生成疗法的进展。尽管存在许多可以提供有关血管生成特定狭窄方面的信息的体外和体内筛选测定，但通常很难解释这些测定结果与生理学相关的3D显微镜组织水平如何与血管生成实际表现出来的情况有关。特别是，由于最终是血管生成的最重要方面，因此缺乏明显的测定方法，这些测定法提供了有关毛细血管形态和功能的直接信息。该建议是用于在原位组织水平上开发高吞吐量3D血管生成测定法。它通过采用高速3D微观成像，多光谱检测，高级组织标记协议以及用于高内容图像分析的软件来实现这一目标。作为第一个应用，我们将其应用于心肌缺血中对成纤维细胞生长因子（BFGF）的血管生成反应。我们认为，该测定法将成为基础研究人员的宝贵工具，并在晚期药物开发过程中为制药公司提供至关重要的信息，以了解是否继续开发候选药物。公共卫生相关性：该提案描述了我们适用于心脏病研究的新的血管生成测定法的发展。它的关键创新是微血管的高度详细的3D图像，以及回到组织生理学，组成和生化状态的能力。它具有降低动物模型中的血管生成测定成本，并提供高生理相关性并提高血管生成疗法治疗心脏病治疗的高生理相关性的强大潜力。