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

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）：血管生成是指现有血管系统中新血管的生长。它涉及许多疾病和学科，包括心脏病，它在心肌梗死后缺血组织的修复中起重要作用。心脏病是美国第二大死因。对缺血性心脏病有效的血管生成疗法的希望已经被一系列令人失望的临床试验所抑制。尽管血管生成很重要，但缺乏有效的血管生成检测方法，这阻碍了血管生成疗法的发展。虽然存在许多体外和体内筛选分析，可以提供血管生成的特定，狭窄方面的信息，但通常很难解释这些分析的结果如何与血管生成实际表现的生理相关3D显微组织水平相关联。特别是，尽管毛细血管形态和原位功能是血管生成最重要的方面，但明显缺乏提供直接信息的检测方法。该建议是为了在原位组织水平上开发一种高通量3D血管生成试验。它通过采用高速3D显微成像、多光谱检测、先进的组织标记协议和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，我们将把它应用于心肌缺血时成纤维细胞生长因子（bFGF）对血管生成的反应。我们相信这项检测将成为基础研究人员的宝贵工具，并在药物开发后期为制药公司提供是否继续开发候选药物的关键信息。公共卫生相关性：本提案描述了一种新的血管生成试验的发展，我们应用于心脏病的研究。它的关键创新是微血管的高度详细的3D图像，并能够回到组织的生理，组成和生化状态。它具有巨大的潜力，可以降低在动物模型中进行血管生成分析的成本，并提供高生理学相关性，并推进血管生成疗法在心脏病治疗中的应用。

项目成果

Serial two-photon tomography for automated ex vivo mouse brain imaging.

• DOI: 10.1038/nmeth.1854
• 发表时间: 2012-01-15
• 期刊: NATURE METHODS
• 影响因子: 48
• 作者: Ragan, Timothy;Kadiri, Lolahon R.;Venkataraju, Kannan Umadevi;Bahlmann, Karsten;Sutin, Jason;Taranda, Julian;Arganda-Carreras, Ignacio;Kim, Yongsoo;Seung, H. Sebastian;Osten, Pavel
• 通讯作者: Osten, Pavel