Prolonged survival of adult rat pancreatic islets transfected with E1A-12Sadenovirus

It has been reported that various mutants of the E1A-adenovirus can activat e quiescent differentiated cells to start proliferating. The aim of this st udy was to determine whether transfection with E1A-12S could extend the lif e span and functionality of pancreatic islets in culture. Rat pancreatic is lets were isolated and transfected with retrovirus containing the adenoviru s E1A-12S, E1A-13S, or control vectors. Transfection with the retroviral E1 A-13S mutant produced extensive islet necrosis compared with nontransfected islets. Islets transfected with the control E1A mutant Ad5-d1312 vector (c ontaining no E1A-12S or E1A-13S segments) were similar to non-transfected i slets in their characteristics. We found that the E1A-12S transfected islet s maintained greater viability, insulin granule structure, and glucose-indu ced insulin responsiveness over a 6-week period compared with mock or contr ol islets. At 6 weeks of culture, the E1A-12S transfected islets also had f ewer apoptotic cells compared with nontransfected islets. These data sugges t that adenovirus E1A-12S can extend the functional life span of cultured r at pancreatic islets.