Generating 3D human models

Professor Margariti leads one of the most advanced induced pluripotent stem cell (iPSC) programmes in the UK. As Director of the iPSC facilities within the Wellcome-Wolfson Institute for Experimental Medicine (WWIEM) at QUB, she oversees a comprehensive pipeline where human iPSCs are generated and differentiated into a wide array of cell types, including endothelial cells, smooth muscle cells, pericytes, cardiomyocytes, neurons, macrophages, retinal pigment epithelial cells, kidney cells, and many others. Her team has also established powerful 2D and 3D vascular and cardiac organoids, including the latest generation of vascularised cardiac tissues, offering unprecedented platforms for human disease modelling, drug discovery, and cell therapy.

In a landmark study published in STEM CELLS in 2024, her group demonstrated the generation of fully functional human blood vessels from both non-diabetic and diabetic patient-derived iPSCs. Using advanced single-cell RNA sequencing, they revealed the precise molecular and transcriptional phenotype that defines diabetic vascular dysfunction. This breakthrough provides a deep mechanistic understanding of vascular disease progression and marks a critical step toward translating patient-specific therapies into the clinic.

Prof Margariti’s lab has made foundational discoveries in vascular reprogramming. Among these, her identification of the RNA-binding proteins QKI-5 and QKI-6 as central regulators of endothelial and smooth muscle cell fate led to the successful generation of functional, layered blood vessels in vitro. A major breakthrough came with the publication of a 2020 study in Nature Communications, which demonstrated that targeting QKI-7 expression in vivo could restore endothelial function in diabetic environments—offering a promising therapeutic strategy for diabetic vascular complications. The team has also created a biobank of diabetic patient-specific iPSC lines using accelerated reprogramming approaches. These lines are now being used to build patient-matched vascular organoids that reflect real human pathologies and enable the development of targeted interventions and novel biomarkers.

Building on these strong foundations, Prof Margariti is now spearheading an ambitious initiative to integrate artificial intelligence and digital twin technologies into her iPSC-based platforms. By combining high-throughput experimental data with machine learning and predictive modelling, her team is creating digital replicas of patient-specific vascular and cardiac systems. These AI-enhanced human models have the potential to revolutionise how diseases are diagnosed, how drugs are tested, and how regenerative therapies are personalised for maximum efficacy and safety.