VASC-ENHANCE: Exploiting Vascular Signals for Enhanced Maturation of iPSC-derived Beta-Like Cells

Type 1 diabetes is a global challenge without a definitive cure, calling for innovative treatment approaches. Human donor islet cell transplantation holds promise, but limited availability, impaired graft revascularization, and lifelong immunosuppression hinder its widespread use. An alternative solution lies in beta-like cells derived from induced pluripotent stem cells (iPSC-ß), which overcome donor scarcity and address immune rejection. However, these lab-grown iPSC-ß cells are functionally immature and need transplantation to acquire adult beta cell characteristics.
Our research investigates the impact of blood vessel-derived signals, specifically Vascular Endothelial Growth Factor-A (VEGF-A) and endothelial cell signaling, on the maturation of iPSC-ß cells. By comprehensive studies on cells cultured in the lab and animal models at islet engraftment sites, we aim to understand how vascular cues influence iPSC-ß cell maturation. We will uncover the underlying mechanisms that drive functional maturation when these cells are transplanted and use this knowledge to optimize the maturation process of iPSC-ß cells.
The findings of our study will significantly advance the field of islet cell transplantation, informing the development of improved strategies for iPSC-ß transplantation. This knowledge will pave the way for more effective cell-based therapies for type 1 diabetes. Unraveling the intricate interplay between VEGF-A, endothelial cells, and iPSC-ß cells will increase our understanding of beta cell biology and refine strategies for successful cell replacement therapy. Ultimately, our research has the potential to revolutionize curative approaches for type 1 diabetes, benefiting children and adults worldwide.