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Engineering vascularised pancreatic islets on a chip to report on the functional connectivity of insulin-producing beta cells

Status: Active
Principal Investigator:
Co-investigators:
  • Joseph Sherwood
    Imperial College London
Researchers:
  • Kinga Suba
    Imperial College London
Award round: 3
Start date: 15-03-2021
End date: 14-06-2021
Contract amount: £16,789
Type 2 Diabetes (T2DM) is amongst the greatest health challenges of our time, now affecting >1 in 11 adults. It results from a failure of insulin secretion from beta cells that reside in thousands of sub millimeter islets spread throughout the pancreas. Understanding how and why this happens is vital for the development of a cure.

We have recently shown that insulin release from islets is orchestrated by a small group of pacemaker beta cells. This raises many questions about how the genetic and nutritional risk factors for T2DM affect co-ordinated beta cell function, and which agents best restore it. The pancreas sits deep inside the abdomen and the tiny islets are impossible to study directly from the outside. Alternatively, islets studied in isolation outside the body are missing the capillary network, which is believed to be crucial in regulating the flow of hormones that underpins beta cell coordination.

We aim to develop a chip that supports islets to grow their own microstructure of blood vessels. This 3D micro-organ will allow us to directly study islet biology, incorporating state-of-the art microscopy alongside a microfluidic system that will precisely deliver nutrients, disease-relevant stimuli and novel drugs. We will build a chip centred around a donor mouse islet to answer how nutrient flow allows beta cells to respond in a coordinated fashion. The potential future applications of such a chip include use of human islets that have been donated to our research programmes. Additionally, stem-cell derived islets from patients with diabetes could be grown on the chip, providing a platform to characterise an individual’s particular disease traits and optimise personalised treatments.

Our team has the understanding of islet implantation biology and cell culture expertise required to achieve vascularisation of an islet on a chip, which has not yet been achieved. This platform could speed up the development of new treatments for diabetes.