A collaborative study led by Professor Maike Sander, Scientific Director of the Max Delbrück Center, has resulted in a vascularized organoid model of pancreatic islets developed from human pluripotent stem cells. Published in Developmental Cell, the research introduces a new model that more closely mimics the cellular environment of human pancreatic islets, potentially offering improvements in diabetes research.
While existing stem cell-derived islet (SC-islet) organoids are widely used, their beta cells often remain immature. By incorporating human endothelial cells and fibroblasts into the SC-islet cultures, the research team was able to generate vascular networks that supported beta cell maturation and insulin secretion. When exposed to high glucose levels, the vascularized islets showed significantly enhanced insulin production compared to their non-vascularized counterparts.
The team identified two primary mechanisms contributing to the observed cell maturation: the formation of an extracellular matrix and the secretion of Bone Morphogenetic Protein (BMP) by endothelial cells. Additionally, the researchers used microfluidic devices to simulate blood flow, which further increased beta cell maturity.
In in-vivo testing, vascularized SC islets transplanted into diabetic mice resulted in improved insulin function and longer-term glycemic control compared to non-vascularized versions. Sander’s group is now applying this model to study immune cell interactions in Type One diabetes by integrating patient-derived immune cells and SC islets on microfluidic chips.
This work offers a more physiologically relevant human model for examining islet function, disease mechanisms, and the effects of immune attack in Type 1 diabetes.
