Use of extra-pancreatic tissues for cell replacement therapy for diabetes

Abstract

Pancreatic islet transplantation may constitute the best approach for the long-term control of blood glucose levels in the treatment of diabetes. However, tissue replacement therapy will become widely available as a treatment for diabetic patients only when islets or insulin-producing cells are available in unlimited amounts, and will not be rejected by the diabetic recipients. The present chapter will analyze the option of using adult extrapancreatic tissues for regulated insulin production. Two major approaches could endow adult extra-pancreatic tissues with characteristics and functions that can be used for diabetes cell replacement therapy: First, insulin gene therapy, which involves the ectopic expression of constructs encoding the proinsulin gene or modified proinsulin sequences in adult extra-pancreatic cells from different sources. Second, the induction of a process called developmental redirection of extra-pancreatic tissues into insulin-producing cells. The second approach exploits the instructive roles of pancreatic transcription and soluble factors in controlling pancreas organogenesis in the embryo to dictate the induction of pancreatic lineage and function also in adult tissues. This approach endows adult extra-pancreatic tissues with pancreatic characteristics and function, thus promoting ex vivo differentiation into insulinproducing and secreting cells. Using adult extra-pancreatic tissues may result in the generation of custom made self surrogate pancreatic beta cells for the treatment of diabetes, bypassing both the shortage in tissue availability from cadaveric donors and the need for life-long immunosuppression. © 2008 Springer.