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Summary of the Project
In a major collaborative effort led by matrix biologist Robert Vernon and immunologist John Gebe, scientists at the Benaroya Research Institute are developing a Bioengineered Implant (BI) for treatment of type 1 diabetes (T1D) – an autoimmune disease. The BI will combine purified islets of Langerhans (the tiny, insulin-producing units of the pancreas) with innovative structural supports made of natural biomaterials.
The BI is designed to provide a controlled microenvironment that promotes the survival and function of the transplanted islets and includes: 1) a permeable extracellular matrix (ECM) hydrogel to provide physical support for the islets and ingrowing vasculature, 2) a sustained-release component that will deliver a set of bioactive compounds that promote islet survival, vascularization, and immunoprotection, and 3) a supportive scaffold to retain the islets, ECM hydrogel, and sustained-release component within a protective, unified structure. The combination of these design elements in a single device represents a novel approach to islet transplantation. The overall goal of this research is to produce a BI that can be implanted into patients in a minimally-invasive manner (perhaps under the skin) and which would eliminate the need for exogenous insulin therapy.
Description of study in researcher’s own words
Islet transplantation can be successful where the donor of the islets and the recipient of the transplant are genetically identical (as in syngeneic strains of mice). However, islet engraftment fails in human patients with T1D as a consequence of: 1) poor shortterm survival of the islets as a result of post-implantation stress, and 2) long-term immune-mediated rejection of the islets caused by tissue mismatches between donor and recipient (alloimmune rejection) and continuance of autoimmunity. Our working hypothesis for this project is that a spectrum of bioactive compounds that promote islet survival, islet vascularization, and protection of islets from host immune attack can be combined in a single device. Importantly, the influence of these compounds would be restricted to the BI and the region immediately surrounding it (using sustainedrelease technology), thereby limiting harmful systemic effects. Advanced versions of the BI might also be used as platforms for patient-derived stem cell transplantation, incorporating bioactive compounds that would promote the survival and differentiation of stem cells into insulin-producing cells.
Roles of the BRI researchers
Dr. Robert Vernon is a matrix biologist and bioengineer who provides the expertise in designing the BI and the system for sustained release of bioactive compounds. His understanding of the importance of revascularization to islet survival is instrumental to the success of this project. Dr. John Gebe is an immunologist with expertise in animal models of T1D. He conducts the hands-on testing of the device in vivo and also determines which immunological systems can be targeted to promote long-term protection of islets from allo- and autoimmune rejection.