Protecting insulin-producing beta cell transplants from death and dysfunction

Diabetes is one of the most common chronic diseases among adults, children and youth. In 2008/09, the Canadian Chronic Disease Surveillance System reported 2,359,252 cases of diagnosed diabetes in Canada and a prevalence of 5.4% in British Columbia. Rates of type 1 diabetes (T1D) among children and youth have been on the rise globally. Poor control of diabetes leads to various complications such as cardiovascular disease, stroke, blindness and renal failure, resulting in a shorter and a reduced quality of life. 

One of the major pathologies in diabetes is a deficiency of insulin, which is secreted from pancreatic beta cells. Patients with T1D require insulin therapy throughout their life because most of their beta cells are destroyed by autoimmune attack. Even through insulin treatment, reduced glycemic control makes complications and hypoglycemia-induced coma more likely.

Islet transplantation is a promising therapy for T1D that removes the need for insulin therapy. However, some limitations remain such as the supply of donor islets, the need for lifelong systemic immune suppression, and graft failure. Today, human embryonic stem cell (hESC)-derived surrogate beta cells are in clinical trials; however, it is likely that these cells will not be protected from immune attack. 

Dr. Sasaki will generate CRISPR-Cas9-edited hESCs that can be differentiated to beta cells that express CCL22 in order to protect hESC-derived islet cell graft from immune attack. If this approach is successful, the results of this study will further the optimization of functional and immune-tolerant surrogate beta cells, which will help pave the way towards a cure for T1D.