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

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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.