DEVELOPMENT OF ENGINEERED PANCREATIC BETA-CELL LINES FOR CELL THERAPYOF DIABETES

Insulin-secreting pancreatic beta-cell lines represent a promising app roach for treatment of insulin-dependent diabetes mellitus (IDDM). Our laboratory has developed a number of highly-differentiate beta-cell l ines in transgenic mice. These cells produce insulin amounts comparabl e to normal pancreatic islets and release it in response to physiologi cal insulin secretagogues. Using a reversible transformation system it has become possible to tightly regulate cell replication in these bet a-cell lines both in culture and in vivo. By employing adenovirus gene s 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 huma n beta-cell lines by genetic engineering of isolated human islets. (C) 1998 Elsevier Science B.V.