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Viral IL-10 gene transfer prolongs rat islet allograft survival

Authors
 Yang-Hee Kim  ;  Dong-Gyun Lim  ;  Yu-Mee Wee  ;  Jin-Hee Kim  ;  Chae-Ok Yun  ;  Monica-Y. Choi  ;  Youn-Hee Park  ;  Song-Cheol Kim  ;  Duck-Jong Han 
Citation
 CELL TRANSPLANTATION, Vol.17(6) : 609-618, 2008 
Journal Title
CELL TRANSPLANTATION
ISSN
 0963-6897 
Issue Date
2008
Abstract
Islet transplantation is a potential cure for diabetes. However, allotransplant rejection severely limits its clinical application. In this study, we sought to transfect rat islets with an adenoviral vector containing the viral IL-10 (vIL-10) gene and examine its efficacy in preventing graft rejection. The immunosuppressive effect of vIL-10 is reported but its efficacy is somehow debatable in transplantation model. vIL-10 transfected islets were transplanted into streptozotocin-induced diabetic rats. Blood glucose, serum vIL-10 concentration, graft histology, and graft cytokine expression were used to monitor graft function up to day 21 after transplantation. Transfected islets released a large amount of vIL-10 protein without affecting their viability and functional integrity. When we transplanted the transfected islets into allogeneic hosts, the survival of grafted islets was not significantly increased. However, the combined use of vIL-10 and subtherapeutic doses of CsA (cyclosporine) significantly prolonged graft survival beyond that achieved with either agent alone (p < 0.001). vIL-10 and CsA-treated rats contain high level of vIL-10 in serum, which is evidenced by the inhibition of allogeneic mixed lymphocyte reaction (MLR). Histological analysis additionally revealed the presence of viable islets up to 21 days. IL-10 mRNA expression in grafted liver was higher and IFN-gamma mRNA was lower in vIL-10 and CsA-treated animals, compared with other groups. The synergistic effect of this combination therapy is potentially correlated with the induction of inhibitory cytokine secretion and downregulation of proinflammatory cytokine secretion from host cells.
Full Text
http://www.ingentaconnect.com/content/cog/ct/2008/00000017/00000006/art00003
DOI
10.3727/096368908786092694
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Yun, Chae Ok(윤채옥)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108514
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