Human blood vessel organoids as models of diabetic vasculopathies

Abstract: Diabetes Mellitus (DM) is a major risk factor for the development of cardiovascular diseases. Patients with DM have increased incidences of microvascular dysfunction, characterised by structural and functional changes in the microvasculature. Typically, endothelial cells (ECs) form tight interactions with pericytes (PCs) to regulate vascular formation and maintain vessel integrity. EC dysfunction and loss of EC-PC interactions, plus dysregulated basement membrane (BM) formation, are key pathological hallmarks associated with DM that promote vascular injury.

Patient-derived induced pluripotent stem cells (iPSCs) from healthy and diabetic donors retain an epigenetic memory. They can therefore be used to generate optimised human-based models which better recapitulate human genetic variation. Such models include human blood vessel organoids (hBVOs), which are self-organising, 3D-structures with striking structural and functional similarities to human microvessels, and iPS-derived ECs (iPS-ECs), which offer a 2D model for studying EC dysfunction.

My project aims to use patient iPSC-derived hBVOs and iPS-ECs to characterise the molecular and functional mechanisms underlying human diabetic vasculopathies. Ultimately, my project aims to generate a model system suitable for high-throughput screening.

Speaker: Aman Pooni

Biography: Aman Pooni is a final year PhD student in the Zampetaki lab at the JBC. She is working with patient iPSC-derived human blood vessel organoids and iPS-ECs to investigate the mechanisms underlying diabetic microvasculopathies.

Host: Anna Zampetaki