Development of engineered pancreatic beta-cell lines for cell therapy of diabetes

Insulin-secreting pancreatic beta-cell lines represent a promising approach for treatment of insulin-dependent diabetes mellitus (IDDM). Our laboratory has developed a number of highly-differentiated beta-cell lines in transgenic mice. These cells produce insulin amounts comparable to normal pancreatic islets and release it in response to physiological insulin secretagogues. Using a reversible transformation system it has become possible to tightly regulate cell replication in these beta-cell lines both in culture and in vivo. By employing adenovirus genes which downreguate antigen presentation and increase cell resistance to cytokines mouse beta cells could be transplanted across allogeneic barriers. These approaches could be applied to the development of human beta-cell lines by genetic engineering of isolated human islets.