Grant: Operating Grant

While islet transplantation is a promising treatment for the 1% of Canadians who live with insulin dependent (type 1) diabetes, the majority of islets (perhaps 60%) in current protocols are lost almost immediately upon transplantation. This is due to inflammatory responses and a failure to make intimate connections between the beta cell (the glucose sensing and insulin making portion of the islet) and the blood vessels of the host. The absence of these vessels near and in the islet impairs islet survival and function. Our approach ("modular tissue engineering") enables the creation of uniform, scalable and most importantly vascularized constructs. Small collagen rods ("modules") are embedded with functional cells (here, pancreatic islets) along with support cells derived from fat tissue and surface seeded with endothelial cells, the cells that line blood vessels. Random packing of many modules creates a porous construct (a "pseudo-fat pad") where the gaps among modules form interconnected channels lined with endothelial cells. Once implanted, the endothelialized channels connect with the host vessels (through a remodelling process) and enable blood flow to nourish the transplanted islets and thereby maintain their viability and function. We expect that this engineered vasculature will also provide at least some of the required intimate contact between the beta cell and the vessels of the host. The specific aims address the fate of modules and islets in diabetic mice and in vitro, the latter using advanced optical imaging methods and custom designed microfluidic chambers made by photolithography as adapted from the processes used to make microelectronic chips. The long-term objective is to enable islet transplantation to be successful.