Bioengineering of Adipocytes

Dr. Peter Light

Peter LightAs of 2013, over 3 million Canadians live with diabetes. Type I diabetes (T1D) accounts for approximately 10% of these cases and is characterized by uncontrolled fluctuations in blood glucose resulting from the destruction of insulin-secreting beta-cells in the islets of the pancreas. A promising transplantation therapy for the treatment of T1D was developed in Edmonton and became known as the “Edmonton Protocol”. While this therapy has been shown to produce insulin independence or a reduced need for insulin in most patients, the scarcity of donor islets and the major problem of immune rejection of the foreign graft need to be overcome. In an attempt to circumvent these problems, we propose to engineer the patients’ own subcutaneous fat cells (white fat cells or adipocytes) to secrete active insulin in a regulated manner. Such an approach could solve the major problems above by 1) avoiding the requirement for large numbers of suitable donor islets and 2) eliminating the need for immunosuppressive strategies. To begin to explore this new approach, we have constructed an adenovirus designed to express and secrete mature insulin in adipocytyes in a controlled manner by employing an optical “on-switch” that is activated by pulses of blue light. In this project we will undertake the first steps to study the properties of these engineered adipocytes with a view to developing a safe and effective cell-based therapy for T1D.