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Curing Type 1 Diabetes

Dr. Alice Tomei, assistant professor in the College of Engineering’s Department of Biomedical Engineering and director of the Islet Immunoengineering Lab at the University of Miami Diabetes Research Institute, received the 2016 Eliahu I. Jury Early Career Research Award for her Type 1 diabetes (T1D) research. Dr. Tomei and her team are developing a novel strategy to increase the applicability of islet transplantation in curing T1D.

T1D is an autoimmune disease in which a person’s pancreas stops producing insulin, a hormone that enables people to get energy from food. It occurs when the body’s immune system attacks and destroys the insulin-producing cells in the pancreas, called beta cells. T1D strikes both children and adults at any age. It comes on suddenly, causes dependence on injected or pumped insulin for life, and carries the constant threat of devastating complications.

Living with T1D is a constant challenge. People with the disease must carefully balance insulin doses—either by injections multiple times a day or continuous infusion through a pump—with eating and other activities throughout the day and night. They must also measure their blood-glucose level by pricking their fingers for blood six or more times a day. Despite this constant attention, people with T1D still run the risk of dangerous high or low blood-glucose levels, both of which can be life threatening.

Islet transplantation eliminates complications of Type 1 diabetes and can restore insulin secretion and glucose homeostasis. Despite the unprecedented clinical success of islet transplantation, the applicability of the procedure is currently limited by the need of chronic immunosuppression.

“One approach to protect transplanted islets without the need for antirejection drugs is to create a protective barrier to hide the islets from the cells of the immune system that otherwise would destroy them,” explains Dr.  Tomei. “We have made significant progress toward this goal, having invented and optimized new technologies to individually coat the islets, thereby camouflaging them from the recipient’s immune system.”

Such technologies allow wrapping the islets with minimal amounts of material to protect them during long-term implantation in the body.

In previous studies conducted by Dr. Tomei and her team, diabetes in mice was reversed in less than one week and the islets continued to function long term, without the use of any anti-rejection drugs. The main goal of our current research projects is to demonstrate that maximizing nutrient transport to the camouflaged islet can improve the outcome of the transplanted cells and allow islet transplantation without immunosuppression in preclinical models of T1D and ultimately in humans.

Our current work on encapsulation will lay the groundwork for future clinical trials of conformal coating encapsulation for islet transplantation without immunosuppression, increasing the safety of the procedure and the applicability to a larger number of T1D patients, including children and young adults. This work is currently funded by two Juvenile Diabetes Research Foundation (JDRF)-sponsored grants and by NIH. Further, Dr. Tomei started evaluating her innovative encapsulation technology with stem cell-derived insulin-secreting cell products in collaboration with Semma Therapeutics (a spin-off of Dr. Doug Melton’s lab at the Harvard Stem Cell Institute) as a part of a sponsored research agreement.

In a parallel track, Dr. Tomei demonstrated that local secretion of the secondary lymphoid-organ chemokine (CCL21) mediates antigen-specific immunological tolerance in cancer and in autoimmune diabetes. She is now translating those findings into a clinically applicable biomaterial platform for co-delivery of CCL21 and beta cell antigens for induction of antigen-specific tolerance. This work is currently funded by one JDRF-sponsored grant.

 

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