Correlative In Vivo Fluorescence and Micro-Computed Tomographic Imaging of Tissue Structure and Function

组织结构和功能的相关体内荧光和显微计算机断层成像

• 批准号: BB/S019480/1
• 负责人: Richard Oreffo
• 金额: $ 71.75万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS019480%2F1
• 关键词: Correlative; Vivo; Fluorescence; Micro; Computed

For human and animal bodies to function properly, the tissues and organs that make them up must be organised properly (have the correct tissue architecture). This must happen across many size scales, from individual cells to large organs such as the liver, kidneys, and bones, or blood vessels and nerves supplying the organs. Given cells and tissues are dynamic three-dimensional (3D) structures, we need to see how they fit together in 3D to understand their architecture, how structures connect and vary within the tissue. For example, in Regenerative Medicine, we try to make tissues and organs to repair damaged and diseased tissues and restore the body to its original health. Scaffolds upon which the cells can grow and are guided are used to help organise the cells into the right structures. We are now in a unique position to create new soft and hard tissues (e.g. liver, neural tissue, cartilage, bone) to improve treatments and to better understand normal and abnormal human and animal body function. Similarly, in aging the composition of our bodies changes, and it is important to be able to track and understand how this happens in living animals, so that ultimately we can have the knowledge to better treat a range of diseases, like heart disease, lung disease and cancer.We are applying for an imaging system that will allow us to examine cells, organs and tissues within the body (called Correlative in vivo imaging) to create 3D images at successive time points, without having to kill the animal to look inside it. The system will allow us to label and follow specific cells and molecules within the body and to create 3D image stacks of tissues of interest with a high-resolution micro-computed tomographic (uCT) imaging device. This uses X-rays to non-destructively image large samples and the design of this new instrument allows us to distinguish individual tissue components and how some of their features change over time, in a way that is not currently possible in two dimensions (2D) through a technique called histology, using normal, light microscopy.The imaging system will add to the wide range of existing imaging facilities in Southampton that are supported by 12 expert imaging staff, employed at the Biomedical Imaging Unit (BIU) and the u-VIS X-ray Imaging Centre (u-VIS). The existing expertise in sample preparation and biological image interpretation is essential for these cutting edge imaging techniques to be used effectively. An additional problem in 3D imaging at all scales is the very large digital image datasets that are produced, each taking large amounts of storage, typically; 50-1000Gb (equivalent of 10-200 DVDs each!). On this account, it is pivotal to have dedicated staff in place who will run and make sure that the imaging system performs efficiently and can provide a reliable, streamlined service to all users. The UoS has agreed to fund a Research Support staff member to underpin and provide a sustainable Imaging Service. Provision of the combined preclinical correlative in vivo imaging system, together with our existing leadership team in advanced computing and image processing (state-of-the-art computing hardware, software and expertise already in place at BIU and u-VIS, will allow investigating and understanding tissue architecture and to understand better tissue function. In this project, we will work with our collaborators in the University to develop further correlative in vivo imaging application areas of tissue samples, specifically including processing and analysis workflows for the 3D datasets. Our ability to understand tissue development and formation in its native 3D context has the potential to transform human health over the next 10-30 years. In order to fulfil this promise, as quickly and safely as possible, it is essential we can image the generated structures and tissues in vivo in a longitudinal fashion and at different hierarchical levels of tissue organisation.

为了使人体和动物体正常运作，组成它们的组织和器官必须正确组织（具有正确的组织结构）。这必须在许多尺寸范围内发生，从单个细胞到大型器官，如肝脏、肾脏和骨骼，或为器官供血的血管和神经。鉴于细胞和组织是动态三维 (3D) 结构，我们需要了解它们如何在 3D 中组合在一起，以了解它们的架构、结构如何在组织内连接和变化。例如，在再生医学中，我们尝试制造组织和器官来修复受损和患病的组织，使身体恢复到原来的健康状态。细胞可以在其上生长并被引导的支架用于帮助将细胞组织成正确的结构。我们现在处于独特的地位，可以创造新的软组织和硬组织（例如肝脏、神经组织、软骨、骨骼），以改善治疗并更好地了解正常和异常的人体和动物身体功能。同样，在衰老过程中，我们身体的成分会发生变化，重要的是能够跟踪和了解活体动物中这种情况是如何发生的，以便最终我们能够获得更好地治疗一系列疾病的知识，如心脏病、肺病和癌症。我们正在申请一种成像系统，该系统将允许我们检查体内的细胞、器官和组织（称为相关体内成像），以在连续的时间点创建 3D 图像，而无需杀死动物 看看里面。该系统将使我们能够标记和跟踪体内的特定细胞和分子，并使用高分辨率微型计算机断层扫描 (uCT) 成像设备创建感兴趣组织的 3D 图像堆栈。它使用 X 射线对大样本进行非破坏性成像，这种新仪器的设计使我们能够区分单个组织成分以及它们的某些特征如何随时间变化，而这种方式目前在二维 (2D) 中无法通过称为组织学的技术，使用正常的光学显微镜。该成像系统将添加到南安普敦现有的各种成像设施中，这些设施由生物医学成像中心雇用的 12 名专家成像人员提供支持。 单位 (BIU) 和 u-VIS X 射线成像中心 (u-VIS)。样品制备和生物图像解读方面的现有专业知识对于有效利用这些尖端成像技术至关重要。所有尺度 3D 成像的另一个问题是生成的数字图像数据集非常大，每个数据集通常占用大量存储空间； 50-1000Gb（相当于每张 10-200 张 DVD！）。因此，拥有专门的工作人员至关重要，他们将负责运行并确保成像系统高效运行，并为所有用户提供可靠、简化的服务。南卡罗来纳大学已同意资助一名研究支持人员，以支持和提供可持续的成像服务。提供组合的临床前相关活体成像系统，与我们现有的先进计算和图像处理领导团队（BIU 和 u-VIS 已有的最先进的计算硬件、软件和专业知识）一起，将有助于研究和了解组织结构并更好地了解组织功能。在这个项目中，我们将与大学的合作者合作，进一步开发组织样本的相关活体成像应用领域，特别包括 3D 数据集的处理和分析工作流程。我们在原生 3D 背景下了解组织发育和形成的能力有可能在未来 10-30 年内改变人类健康。为了尽可能快速、安全地实现这一承诺，我们必须能够以纵向方式和组织组织的不同层次水平对体内生成的结构和组织进行成像。

项目成果

Endothelial Cells: Co-culture Spheroids.

内皮细胞：共培养球体。

• DOI: 10.1007/978-1-0716-0916-3_5
• 发表时间: 2021
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Kanczler JM

A blueprint for translational regenerative medicine.

• DOI: 10.1126/scitranslmed.aaz2253
• 发表时间: 2020-12-02
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Armstrong JPK;Keane TJ;Roques AC;Patrick PS;Mooney CM;Kuan WL;Pisupati V;Oreffo ROC;Stuckey DJ;Watt FM;Forbes SJ;Barker RA;Stevens MM
• 通讯作者: Stevens MM

Growth-Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

刺激骨形成的无生长因子多组分纳米复合水凝胶

• DOI: 10.1002/adfm.201906205
• 发表时间: 2020-02-16
• 期刊: ADVANCED FUNCTIONAL MATERIALS
• 影响因子: 19
• 作者: Okesola, Babatunde O.;Ni, Shilei;Mata, Alvaro
• 通讯作者: Mata, Alvaro