Role of fibrin-integrin interactions in supporting 2D and 3D pancreatic islet growth and function

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The discovery of insulin in 1921 by Banting and Best laid the foundation for the modern management of diabetes mellitus. However, insulin treatment cannot cure diabetes and will not prevent the secondary complications that are responsible for the devastating morbidity and mortality of this disease. Replacement of insulin-producing cells through islet transplantation has the best chance to prevent, reverse or stabilize these complications. However, the scarcity of islets and limitations in our knowledge of the factors influencing islet biology present a major obstacle precluding islet transplantation from being adopted as a routine treatment. Advancement in this field requires a thorough understanding of the developmental biology of the pancreas. In the present application we propose to identify specific factors that are responsible for the maintenance of insulin-producing cells. Our focus is on the role of integrins, membrane receptors that are known to interact with extracellular matrix proteins to control several aspects of pancreatic organogenesis and tissue maintenance. We will characterize these receptors on insulin-producing cells, examine their interactions with one specific matrix protein, fibrin, and study the mechanisms by which these interactions regulate survival of insulin-producing cells. It is our hope that these studies will facilitate the development of appropriate tissue engineering strategies for a bioartificial endocrine pancreas. This treatment will have far-reaching economic and social benefits.