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Continuing the Search for a Type 1 Diabetes Cure

Type 1 diabetes (T1D) is an autoimmune disease in which a person’s pancreas stops producing insulin, a hormone that enables people to get energy from food. The disease, which affects more than 3 million Americans, occurs when the body’s immune system attacks and destroys the insulin-producing cells in the pancreas called beta cells.

Without beta cells, insulin is not produced, resulting in high levels of glucose remaining in the bloodstream, which can damage blood vessels and vital organs over time. People with the disease must carefully balance insulin doses – either by injections multiple times a day or by continuous infusion through a pump – while eating and performing other activities throughout the day and night.

Replacement of pancreatic islets through transplantation may cure T1D, but it requires lifelong immunosuppression. “When you transfer the islets from one patient to another, the immune system of the patient that received the islets will recognize the graft as foreign and will attack and kill the islets, just as they do for viruses and bacteria,” explains 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 (DRI).

To prevent the destruction of the graft, a patient would have to use anti-rejection drugs to suppress the body’s immunoresponse, but anti-rejection drugs have a lot of side effects. Encapsulating the pancreatic islets with a protective covering may allow transplantation without immunosuppression and promote long-term islet graft function and survival.

“The idea is to place a barrier to hide and protect the transplanted cells,” Tomei says. “However, the encapsulation must not be impenetrable as this will deprive the islets from the oxygen and nutrients they need to survive.”

In previous research projects, Tomei and her team 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.

The National Institutes of Health (NIH) – one of the world’s foremost medical research centers – awarded Tomei a grant of over $2 million to continue her breakthrough research on encapsulation of pancreatic islets. The research project, entitled “Conformal Islet Encapsulation for Transplantation at Vascularized Sites to Allow Physiological Insulin Secretion,” is a cross-campus collaboration, involving Peter Buchwald, an associate professor at the Department of Molecular and Cellular Pharmacology and the director of the Drug Discovery Program at the DRI; Allison Bayer, a research assistant professor in the Department of Microbiology and Immunology and the DRI; and Diana Velluto, an associate scientist with chemistry and nanotechnology expertise at the Islet Immunoengineering Lab.

The new research project will test a recently developed encapsulation technology that “conforms” to the size and shape of the individual islet rather than enclosing them in fixed-diameter traditional capsules. “The conformal coating not only reduces the diffusion distance between the islets and the body, increasing nutrient transport, but also reduces the overall graft volume more than 100-fold, making possible transplantation in well-vascularized sites, further maximizing nutrient transport,” Tomei says.

“An increase in nutrient transport results in faster reaction times for the islets to release insulin,” she continues. “The best part, however, is that the conformal coating can be used with insulin-producing cells derived from stem cells that essentially secrete an unlimited amount of insulin. We want to see if our unique coating technology will successfully allow long-term diabetes reversal in preclinical models of diabetes using these cells.”

The project will also focus on using innovative nanomaterials to provide local immunomodulation (the regulatory adjustment of the immune system) in the immediate post-transplant period, minimizing the number of cells needed to reverse T1D and maximizing long-term graft function.

“The work in the preclinical models proposed in this five-year project is needed before we can test our base and nanomaterial-refined conformal coating platform in large preclinical models and then in humans,” Tomei says.

To learn more about the Islet Immunoengineering Laboratory and Tomei’s other research projects, please click here.

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