Tissue engineering of the human thymus: developing the optimal scaffold through integrating biological protocols with advanced imaging

人类胸腺组织工程：通过将生物方案与先进成像相结合来开发最佳支架

• 批准号: 2722998
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2722998
• 关键词: Tissue; engineering; human; thymus; developing

The thymus plays an important role in the development of the immune system.Congenital athymia is a condition whereby the thymus is absent, with life-threateningimplications. Thymic tissue engineering (i.e., creation of artificial organs in the lab)could lead to new treatments for this condition. Moreover, an artificial thymus may beutilised for ex vivo production of functional T cells for acquired congenital deficiencies,cancer therapies and immune tolerance in autoimmunity. We previously showed that adecellularised thymic extracellular matrix (ECM) allows rebuilding a functional humanthymus with cultured thymic stromal cells. Decellularised ECM has several advantagessuch being clinically relevant, biocompatible, and promoting cell-to-cell organisationfor proper compartmentalisation. However, this ECM shows batch-to-batch variabilityand is not ideal for ex vivo systems that shall require scalability for tailoredapplications. In this project the student will test the ability of primary stromal cells toreorganise within customised biomaterials to re-create a 3D scalable and reproduciblemicroenvironment that promotes functional T-cell development. Imaging isinstrumental to the development of such approaches and the goal of this project is toexploit the latest developments in advanced imaging technology to generate detailedinformation on scaffolds and recellularization processes that will allow refiningmethods for engineering the thymus. Since imaging techniques commonly used forthis purpose (SEM, histology) are essentially destructive, hence they do not qualify forwhole-tissue 3D imaging, we will apply x-ray micro-CT. The strength of the latter is itshigh penetration depth, micrometric spatial resolution and the generation of 3Dimages non-destructively. The student will collaborate with the Advanced X-RayImaging group at UCL Medical Physics, where cutting-edge x-ray technology is beingdeveloped, and apply those methods to engineered thymi for the first time. The imagedata will provide feedback on the biological protocols applied, enabling their iterativerefinement.

胸腺在免疫系统的发育中起着重要的作用。先天性肌无力是一种胸腺缺失的情况，具有生命威胁。胸腺组织工程(即在实验室中创造人工器官)可能会带来治疗这种疾病的新方法。此外，人工胸腺可能被用于体外产生功能性T细胞，用于后天先天缺陷、癌症治疗和自身免疫中的免疫耐受。我们之前的研究表明，脱细胞胸腺细胞外基质(ECM)可以用培养的胸腺基质细胞重建具有功能的人胸腺。脱细胞ECM有几个优点，如临床相关、生物相容，以及促进细胞间的组织以实现适当的分区。然而，这种ECM表现出批次到批次的可变性，对于需要为定制应用程序提供可伸缩性的体外系统来说并不理想。在这个项目中，学生将测试原始基质细胞在定制的生物材料中重组的能力，以重建一个3D可扩展和可重现的微环境，促进功能T细胞的发育。成像对这种方法的发展是有帮助的，这个项目的目标是利用先进成像技术的最新发展来产生关于支架和再细胞过程的详细信息，这将使改进胸腺工程的方法成为可能。由于通常用于这一目的的成像技术(扫描电子显微镜、组织学)本质上是破坏性的，因此它们不符合全组织3D成像的条件，因此我们将应用X光微型CT。后者的优点是具有较高的穿透深度、微米空间分辨率和非破坏性地生成三维图像。这名学生将与伦敦大学学院医学物理的高级X射线成像小组合作，并首次将这些方法应用于工程胸腺。UCL医学物理正在开发尖端的X射线技术。ImageData将提供有关应用的生物方案的反馈，使其能够迭代完善。