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Titolo:
IMPROVED SURVIVAL OF BIOLISTICALLY TRANSFECTED MOUSE ISLET ALLOGRAFTSEXPRESSING CTLA4-IG OR SOLUBLE FAS LIGAND
Autore:
GAINER AL; SUAREZPIZON WL; MIN WP; SWISTON JR; HANCOCKFRIESEN C; KORBUTT GS; RAJOTTE RV; WARNOCK GL; ELLIOTT JF;
Indirizzi:
UNIV ALBERTA,DEPT MED MICROBIOL & IMMUNOL,HERITAGE MED RES CTR 621 EDMONTON AB T6G 2S2 CANADA UNIV ALBERTA,DEPT MED MICROBIOL & IMMUNOL,HERITAGE MED RES CTR 621 EDMONTON AB T6G 2S2 CANADA UNIV ALBERTA,SURG MED RES INST EDMONTON AB T6G 2S2 CANADA UNIV ALBERTA,DEPT SURG EDMONTON AB T6G 2S2 CANADA UNIV ALBERTA,DEPT MED EDMONTON AB T6G 2S2 CANADA
Titolo Testata:
Transplantation
fascicolo: 2, volume: 66, anno: 1998,
pagine: 194 - 199
SICI:
0041-1337(1998)66:2<194:ISOBTM>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC-ISLETS; GRAFT-REJECTION; CELL ACTIVATION; CD95 LIGAND; TOLERANCE; MICE; PREVENTION; APOPTOSIS; INDUCTION; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
A.L. Gainer et al., "IMPROVED SURVIVAL OF BIOLISTICALLY TRANSFECTED MOUSE ISLET ALLOGRAFTSEXPRESSING CTLA4-IG OR SOLUBLE FAS LIGAND", Transplantation, 66(2), 1998, pp. 194-199

Abstract

Background, Pancreatic islet transplantation is limited because of immune rejection of the transplanted tissue. Long-term survival of allogeneic pancreatic islet grafts in the absence of systemic immunosuppressive agents should be possible by transfecting the islets directly with DNA encoding immunoregulatory molecules. Localized production of these molecules should affect only the immune cells that come into the vicinity of the foreign tissue. We investigated whether local expressionof human CTLA4-Ig or soluble human Fas ligand from biolistically transfected mouse islets would have a protective effect on allograft survival. Methods. Isolated CBA (H2(k)) islets were biolistically transfected using the gene gun. The experimental groups were naked gold particles (n=6), empty vector DNA (n=5), DNA encoding human CTLA4-Ig (n=8), or soluble human Fas ligand (n=5). Secretion of the transfected gene product was confirmed by screening islet culture supernatants for protein production using a sandwich ELISA, The blasted islets were transplanted under the kidney capsule of alloxan-diabetic BALB/c (H2(d)) recipients. Results. Control grafts survived for 23 days, on average. CTLA4-Ig-transfected islets showed a bimodal distribution: 50% of cases survived greater than or equal to 46 days and 50% were similar to the controls. In the soluble human Fas ligand group, 80% of grafts survived greater than or equal to 50 days. There was no correlation between graftsurvival times and pretransplant levels of protein production. Conclusion. Our results indicate that local production of human CTLA4-Ig or soluble human Fas ligand by biolistically transfected islets can promote allograft survival. This approach should be valuable as a potentialimmunoprotective therapeutic strategy in tissue transplantation.

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Documento generato il 05/12/20 alle ore 23:40:11