Generating human diabetic blood vessel organoids as a powerful model to investigate and treat the diabetic vasculopathy

In this project induced pluripotent stem cells will be derived diabetic patient specific blood vessel organoids. The function and signalling of diabetic vascular organoids will be assessed to dissect the profile of vasculopathy in diabetes and deliver new knowledge, biomarkers and effective therapies for vascular complications.

There is an urgent need to develop robust human models to investigate the mechanisms of vascular complications in diabetes. These models will also reduce and replace the animals used. One of the most deleterious events in diabetes, at the levels of the micro- and macro- vasculature, is endothelial cell dysfunction and blood vessels damage. In particular, major diabetic complications are the consequence of blood vessel pathologies, such as reduced capillary densities and thickening of the basement membrane. However, better models (both from human origin and 3D structure) are needed to study these pathologies. In this study we will test the hypothesis whether blood vessel organoids derived from induced pluripotent stem cells from diabetic patients, are attractive models to investigate the underlying mechanisms of diabetic vasculopathy. This hypothesis will be evaluated through the following specific 3 aims:

Aim 1: To fully characterise the blood vessels organoids derived from diabetic iPS cells.

Aim 2: To perform single cells analysis of the derived blood vessel organoids.

Aim 3: To validate key findings of the single cells analysis and perform functional profiling. The findings of this study will contribute to development of new biomarkers for the disease, and the discovery of novel therapeutic interventions.

Start Date: October 2022