Investigating different components of the foetal liver in supporting haematopoiesis and for engineering the human foetal liver microenvironment in vitro

Haematopoietic stem cell (HSC) transplantation is a curative therapy for blood cancers and immune disorders, but its success is limited by low engraftment rates and the inability to expand HSCs efficiently in vitro. During embryogenesis, the human foetal liver (FL) is the primary site for HSC expansion, yet the cellular and extracellular mechanisms that enable this remain poorly understood. This project aims to characterise key stromal components of the FL niche: hepatoblast-derived organoids, foetal fibroblasts, and endothelial cells—together with the extracellular matrix (ECM), across 8–20 post-conception weeks. Preliminary findings reveal stromal heterogeneity, stage-specific cytokine expression, and dynamic ECM remodelling, suggesting coordinated signals underpin HSC support. Building on this, we will reconstruct a bioengineered FL niche in vitro using 3D collagen scaffolds seeded with stromal populations and supplemented with ECM proteins identified by proteomics. This system will be tested for its ability to maintain and expand HSCs ex vivo, with functional assessment by molecular assays and, if feasible, transplantation studies. By uncovering the developmental principles of the FL niche and recreating them in vitro, this research aims to establish a platform for improving HSC expansion, ultimately enhancing accessibility and outcomes of stem cell transplantation.