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

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-threatening
implications. 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 be
utilised for ex vivo production of functional T cells for acquired congenital deficiencies,
cancer therapies and immune tolerance in autoimmunity. We previously showed that a
decellularised thymic extracellular matrix (ECM) allows rebuilding a functional human
thymus with cultured thymic stromal cells. Decellularised ECM has several advantages
such being clinically relevant, biocompatible, and promoting cell-to-cell organisation
for proper compartmentalisation. However, this ECM shows batch-to-batch variability
and is not ideal for ex vivo systems that shall require scalability for tailored
applications. In this project the student will test the ability of primary stromal cells to
reorganise within customised biomaterials to re-create a 3D scalable and reproducible
microenvironment that promotes functional T-cell development. Imaging is
instrumental to the development of such approaches and the goal of this project is to
exploit the latest developments in advanced imaging technology to generate detailed
information on scaffolds and recellularization processes that will allow refining
methods for engineering the thymus. Since imaging techniques commonly used for
this purpose (SEM, histology) are essentially destructive, hence they do not qualify for
whole-tissue 3D imaging, we will apply x-ray micro-CT. The strength of the latter is its
high penetration depth, micrometric spatial resolution and the generation of 3D
images non-destructively. The student will collaborate with the Advanced X-Ray
Imaging group at UCL Medical Physics, where cutting-edge x-ray technology is being
developed, and apply those methods to engineered thymi for the first time. The image
data will provide feedback on the biological protocols applied, enabling their iterative
refinement.