Karen Cosgrove, BSc, PhD, MRSB

Stem Cells and Diabetes Mellitus

The potential of transplantation-based therapy for the cure of diabetes mellitus is limited by the lack of suitable organ donors and the unsuitability of alternative cell sources (e.g. xenotransplantation of porcine tissues). This problem may be overcome by deriving new insulin-secreting cells from human embryonic stem (hES) cells, adult stem cells or induced pluripotent stem cells. We are using hES cell lines and adult stem cells - generated to comprehensive ethical and regulatory criteria - for the production of insulin-secreting cells. Cells are differentiated using novel techniques including 3-dimensional approaches to mimic the pancreatic niche.  The molecular and physiological properties of the human stem cell-derived insulin-secreting cells are compared in detail with those of native human insulin-secreting cells to ensure that the derived cells fully replicate the function of native cells. We aim to derive insulin-secreting cells which are glucose-responsive and regulate the production of insulin in a physiologically relevant manner. In the future hES-derived insulin secreting cells could be used in transplantation therapy to treat diabetes mellitus.

Congenital Hyperinsulinism of Infancy (CHI)

Congenital Hyperinsulinism in Infancy (CHI) is a rare disease of the newborn resulting in dangerously low blood sugar levels. Babies with the disorder are treated using medical therapies such as diazoxide and somatostatin, but when this fails a partial pancreatectomy is required to prevent further hypoglycaemia. Using tissue isolated during pancreatectomy we are able to study the pathogenesis of the condition using techniques such as live cell Ca²⁺ imaging, patch-clamp electrophysiology, immunohistochemistry, gene microarrays and quantitative PCR. In addition we have created cell-lines from the tissue which represent unique tools to study this disease further. Using these techniques we have previously shown that defects in the function of ion channels in pancreatic beta-cells explain many cases of CHI and that some patients may respond to therapy with nifedipine, a voltage-gated Ca²⁺ channel antagonist.  Our ongoing studies aim to further characterise the physiological function of pancreatic beta-cells in CHI and identify new targets for treatment. Our lab is part of the Northern Centre for the treatment and study of hyperinsulinism (NorCHI) and we work closely with the clinicians involved in the day-to-day care of these patients.

Diabetes mellitus affects 2.8 million people in the UK and is becoming increasingly common. It occurs when the body loses the ability to control blood sugar levels, either due to a lack of the hormone insulin (Type 1 diabetes) or due to insulin resistance (Type 2 diabetes). My lab investigates the processes which control how and when insulin is released from the pancreas. In order to treat Type 1 diabetes, pancreatic islet transplantation is available for a small number of patients but there will always be a mismatch in the number of patients who could potentially benefit from this treatment and the amount of pancreatic donor material which is available. Hence another area of research is to identify alternative sources of insulin-producing cells which could ultimately be used for transplantation. At the present time we are investigating the use of human embryonic stem cells and human adult stem cells as potential sources of islet tissue. My lab also has a very active interest in Congenital Hyperinsulinism of Infancy (CHI), which is characterised by extremely low blood sugar levels. We work with colleagues at Royal Manchester Children’s Hospital to understand more about this rare disease and find alternative treatments.