November 2016 — Dr. Alice Tomei, director of the DRI’s Islet Immunoengineering Laboratory, and her team have pioneered research to engineer new therapies for type 1 diabetes (T1D). A key project is the development and implementation of an innovative encapsulation platform technology for insulin-producing cells, which is designed to overcome the many limitations of islet encapsulation. Similar to shrink-wrapping, these “conformal” coatings individually cloak each transplanted islet, which are different shapes and sizes, with an ultra-thin barrier to camouflage them from the recipient’s immune system.
Protecting transplanted insulin-producing cells is critical for sustaining their long-term survival and function because there are two immune system-related forces at work in type 1 diabetes (T1D). First, when a foreign organ or cell is transplanted into the body, the immune system will recognize that this is not its own “self” and take measures to reject it. Second, the transplanted insulin-producing cells will be destroyed by the same autoimmune attack that caused T1D. The ability to successfully transplant encapsulated islets may overcome these immune system challenges and do so without the need for anti-rejection drugs.
Dr. Tomei’s team has already demonstrated that conformal coated islets provide a smaller volume for transplant – the coated islets are similar in size to non-coated (naked) islets, which can reduce the total volume of transplanted cells. They also showed that conformal coatings do not delay insulin release in response to changes in blood sugar while allowing sufficient and much-needed oxygen to enter the cells. Finally, they demonstrated that conformal coated islets can reverse hyperglycemia and function in experimental models of diabetes for more than 100 days. Recently, the team has focused on optimizing the coatings with islets and with stem cell-derived insulin-secreting cells.
Thanks to the ongoing funding provided by the Diabetes Research Institute Foundation, in addition to several new grants awarded by the JDRF, Semma Therapeutics, and the NIH (National Institutes of Health), including a prestigious JDRF career development award, Dr.Tomei and her team will take the next series of steps to advance this work with the final goal of testing the technology in clinical trials of islet transplantation without the use of immunosuppression. In the next phase of their studies, they will test the conformal coated islets in experimental models that more closely mimic the T1D disease process in humans, including preclinical studies in collaboration with DRI colleagues Drs. Dora Berman-Weinberg and Norma Kenyon.
Building on the expertise of assistant scientist and chemist Dr. Diana Velluto, the team will also refine the conformal coating platform technology to include oxygen carriers and agents to reduce inflammation, stimulate the growth of blood vessels, and provide further protection within the transplant site.
In a related arm of this research that has also been awarded JDRF funding, Dr. Tomei has teamed up with two DRI immunologists, Dr. Allison Bayer, research assistant professor of microbiology andimmunology, co-principal investigator of the grant, and with Dr. Alberto Pugliese, director of immunogenetics and co-investigator. The team will work to engineer implantable biomaterials incorporating CCL21, a particular molecule that has been shown to promote immunetolerance, together with engineered hydrogels, gel-tethered fusion proteins, and other target molecules that may help establish tolerance.
“We need to demonstrate efficacy of conformal coatings in spontaneous models of diabetes and in larger models of T1D before moving to humans, as well as scale-up the fabrication process to allow encapsulation of hundreds of thousands of islets in a short amount of time.” said Dr.Tomei. “We are grateful for the significant support that will keep our work moving forward to benefit people living with T1D.”
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Lori Weintraub, APR