Developing a human vascularised pancreatic islet on a chip - VIOC

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Maintaining blood sugar levels within a remarkably narrow range despite large variations in how much we eat or exercise is one of the marvels of the human body. Two hormones each with opposing effects, glucagon and insulin, are the main regulators of blood sugar. They are released from tiny "islets" that are dispersed throughout the pancreas. Islet cells constantly sense sugar levels in the blood and respond in a finely tuned manner to release the right mix of insulin and glucagon to tightly control our blood sugar levels. There remain fundamental gaps in our understanding of how islets work in healthy people to regulate blood sugar. Furthermore, discovering how to restore these mechanisms in patients with diabetes, now affecting over 1 in 11 adults, is essential if we are to find a cure for the disease.We have recently shown that the hormone secreting cells within the islets are connected and communication between them is essential for orchestrating healthy insulin release. To date most of our understanding about islet function comes from rodent studies, since human islets are too small to radiologically image and the pancreas is too deep and dangerous to biopsy. However, the relative positions of the different hormone-secreting cell types differs quite markedly between human and rodent islets and the blood circulation is different too. This limits our ability to make conclusions about human islet function from rodent studies. Some labs are able to perform experiments on islets donated to medical research by people who have died. However, in a petri dish with culture medium these precious islets quickly die. We are unable re-create the important element of blood flow through capillaries within the islet that carry in nutrients (like sugar) and pass on important hormonal messages within the islet itself and beyond. Therefore the aim of this project is to extend the life and utility of donor human islets in a device that supports the islets to become embedded and ultimately vascularised in a bed of human capillaries. This "vascularised islet on a chip" or VIOC will allow us to circulate nutrients through the blood vessel network and through the islet, keeping it alive for much longer than is now possible. The chip will be transparent so that we can examine the responses of human islets under the microscope in real-time and it can also be linked to hormone measuring devices to achieve readouts of hormone secretory function. VIOC will allow us to study human islet function in response to a range of experiments that could help us answer fundamental questions that are still unknown - for example whether specific nutrients (breakdown products of fat or protein metabolism) have particular benefits on insulin secretion or how the immune system interacts with islets to protect them from damage. We will work with our network of collaborators in the field of islet biology to validate VIOC as an effective and indeed superior replacement for rodents to interrogate islet function in health and disease.