Developing a Personalized Drug Screening Platform for Diabetic Microangiopathy

Microangiopathy is a major complication in diabetes mellitus with a pronounced impact on microvascular perfusion, vessel rarefaction and tissue ischemia. In the microvessels, endothelial cells and pericytes are in direct contact, forming complex networks and depositing the basement membrane. Using human blood vessel organoids (BVOs) we recently demonstrated that they capture key aspects of the microvasculature and respond rapidly to metabolic rewiring. Employing two different models of diabetes, we find that diabetic BVOs display loss of endothelial cell- pericyte interaction, thickening of the basement membrane and decreased endothelial cell proliferation, all functional features also readily observed in diabetic clinical microvascular specimens. Here we will utilize diabetic patient-derived BVOs to establish a functional screening platform that will enable personalized therapeutic approaches. Our aim is to uncover novel events in diabetic microangiopathy that can be targeted pharmacologically to restore the function of the microvasculature. This pipeline will serve as a personalized system to test existing and new medications to identify effective drugs for each diabetic patient.