SOTA: Harnessing Regenerative Medicine to Restore Beta-cell Function in Diabetes (Interactive Session)

All forms of clinical diabetes in humans are characterised by at least relative deficiency of pancreatic insulin secretion. As we celebrate the centenary of the discovery and clinical introduction of life-saving insulin therapy, diabetes remains a leading cause of blindness, end-stage renal failure and non-traumatic leg amputation. It is well-established that these complications can be prevented by successful limitation of chronic high glucose exposure. Even short term exposure to low glucose can, however, rapidly lead to loss of normal awareness of hypoglycaemia and dangerous events requiring help from others in treatment, however.

The bioartificial pancreas linking continuous glucose sensing to subcutaneous insulin pump therapy in a ‘closed loop’ is beginning to offer the real potential of more near-normal glucose levels but this approach will never remove the burden of ongoing self-management and remaining risk of decompensated high and low glucose levels.

Transplantation of a whole deceased donor pancreas together with its blood supply can completely normalise glucose levels but this major operation is associated with unavoidable mortality risk and is thus largely reserved for those also receiving a simultaneous kidney transplant. The insulin producing islets from donor organs can, however, be isolated and infused through a minimally invasive procedure which has been fully funded by the NHS as a life-saving procedure for severe hypoglycaemia since 2008.

Advances in regenerative medicine including cell therapy, gene therapy and tissue engineering offer the realistic potential of achieving reproducible and sustainable insulin independence after a single transplant procedure. Converting beta-cell transplantation into a viable truly curative option for much larger numbers of recipients will be dependent on avoiding the need for life-long immunosuppression.

Increased access to primary human pancreatic tissue has confirmed presence of residual beta-cells in the majority with diabetes including many with insulin dependent type 1 diabetes. This has fuelled efforts to elucidate the mechanisms underlying loss of beta-cell function towards new therapeutic approaches to restore insulin secretion in the endogenous pancreas without transplantation.