In vitro-generation of surrogate islets from adult stem cells.

Type 1 diabetes is one of the more costly chronic diseases of children and adolescents throughout North America and Europe, exhibiting an average estimated prevalence rate of nearly 0.2%. It occurs in genetically predisposed individuals when the immune system attacks and destroys specifically the insulin-producing beta cells of the pancreatic islets of Langerhans. While routine insulin therapy can provide diabetic patients with their daily insulin requirements, non-compliance and undetected hyperglycemic excursions often lead to subsequent long-term microvascular and macrovascular complications. The only real cure for type 1 diabetes is replacement of the beta cell mass, currently being accomplished through ecto-pancreatic transplantation and islet implantation. Both of these procedures suffer from a chronic shortage of available donor tissue in comparison to the number of potential recipients. To circumvent this need, three alternative approaches are being intensively investigated: (1) the production of surrogate cells by genetically modifying non-endocrine cells to secrete insulin in response to glucose challenge; (2) the trans-differentiation of non-endocrine stem/progenitor cells or mature cells to glucose-responsive adult tissue; and (3) the regulated differentiation of islet stem/progenitor cells to produce large numbers of mature, functional islets. In recent years, each of these approaches has made impressive advances, leading to the most important question, 'how soon will this new science be available to the patient?' In the present review, we discuss some of the recent advances, focusing primarily on the differentiation of islet stem cells to functional endocrine pancreas that may form the basis for future treatment. Copyright 2004 Elsevier B.V.