Prolonged survival of adult rat pancreatic islets transfected with E1A-12S adenovirus.
It has been reported that various mutants of the E1A-adenovirus can activate quiescent differentiated cells to start proliferating. The aim of this study was to determine whether transfection with E1A-12S could extend the life span and functionality of pancreatic islets in culture. Rat pancreatic islets were isolated and transfected with retrovirus containing the adenovirus E1A-12S, E1A-13S, or control vectors. Transfection with the retroviral E1A-13S mutant produced extensive islet necrosis compared with nontransfected islets. Islets transfected with the control E1A mutant Ad5-dl312 vector (containing no E1A-12S or E1A-13S segments) were similar to nontransfected islets in their characteristics. We found that the E1A-12S transfected islets maintained greater viability, insulin granule structure, and glucose-induced insulin responsiveness over a 6-week period compared with mock or control islets. At 6 weeks of culture, the E1A-12S transfected islets also had fewer apoptotic cells compared with nontransfected islets. These data suggest that adenovirus E1A-12S can extend the functional life span of cultured rat pancreatic islets.
Rutten
M J
MJ
Department of Surgery, Oregon Health Sciences University, Portland 97201, USA. ruttenm@ohsu.edu
Lester
L R
LR
Quinlan
M P
MP
Meshul
C K
CK
Deveney
C W
CW
Rabkin
J M
JM
D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000502:physiology / Q000648:ultrastructure; D005822:Genetic Vectors; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D017500:Adenovirus E1A Proteins; D007328:Insulin; D010446:Peptide Fragments; D011994:Recombinant Proteins