详细记录  
题名:Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets.
作者:CHAE HY; LEE M; HWANG HJ; KIM HA; KANG JG; KIM CS; LEE SJ; IHM SH;
来源:Transpl Int. 2013 Apr;26(4):443-52. doi: 10.1111/tri.12052. Epub 2013 Jan 24. [ IF= 0.00 ] ]
URL :10.1111/tri.12052
日期:20130430
摘要:Glucagon-like peptide-1 (GLP-1) stimulates cell proliferation and has
anti-apoptotic effects on pancreatic islet beta cells. In our previous study, the
transduction of mouse islets with a recombinant adenovirus containing GLP-1 cDNA
enhanced islet graft survival. In this study, we sought to deliver the GLP-1 gene
using a nonviral vector, which raises fewer safety issues in clinical
application. We constructed a plasmid, pbeta-SP-GLP-1, in which a secretion
signal peptide (SP) was inserted to increase GLP-1 secretion, and transfected
mouse islets using the nonviral carrier Effectene. Transfection of pbeta-SP-GLP-1
induced a significant increase in bioactive GLP-1 levels in islet cultures.
Islets transfected with pbeta-SP-GLP-1 were protected from H2 O2 -induced cell
damage in vitro. In addition, glucose-stimulated insulin secretion was
significantly increased in pbeta-SP-GLP-1-transfected islets. Diabetic syngeneic
mice transplanted under the kidney capsule with a marginal mass of
pbeta-SP-GLP-1-transfected islets rapidly became normoglycemic, with 88% of
recipients being normoglycemic at 30 days post-transplantation compared with 52%
of mice that received pbeta-transfected islet grafts (P < 0.05). Islet grafts
retrieved 7 days after transplantation revealed that the
pbeta-SP-GLP-1-transfected group had significantly more Ki67-positive cells as
compared with the pbeta-transfected group. In conclusion, delivery of a plasmid
containing a secretion SP and GLP-1 cDNA using a nonviral carrier leads to
efficient secretion of GLP-1 in mouse islet cells, enhances islet cell survival
during the early post-transplant period, and improves islet transplantation
outcome.

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