ArticlePharmaceutical research2009
Bipartite adenoviral vector encoding hHGF and hIL-1Ra for improved human islet transplantation.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Improved therapeutic potential of MSCs by genetic modification.Gene therapy · 2018Review
- Mesenchymal stem cell-based therapy.Molecular pharmaceutics · 2013Review
- Genetically modified human bone marrow derived mesenchymal stem cells for improving the outcome of human islet transplantation.PloS one · 2013Article
- RGD peptide-modified adenovirus expressing hepatocyte growth factor and X-linked inhibitor of apoptosis improves islet transplantation.The journal of gene medicine · 2011Article
- Genetically modified mesenchymal stem cells for improved islet transplantation.Molecular pharmaceutics · 2011Review
- Mesenchymal stem cells as a gene delivery vehicle for successful islet transplantation.Pharmaceutical research · 2011Article
- Genetic vaccination for re-establishing T-cell tolerance in type 1 diabetes.Human vaccines · 2011Review
- XIAP gene expression protects β-cells and human islets from apoptotic cell death.Molecular pharmaceutics · 2010Article
- Article
- Gene therapy in diabetes.Self/nonself · 2010Article
- Gene expression and silencing for improved islet transplantation.Journal of controlled release : official journal of the Controlled Release Society · 2009Review
- RNA interference for improving the outcome of islet transplantation.Advanced drug delivery reviewsReview
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeEx vivo gene therapy can improve the outcome of islet transplantation for treating type I diabetes. Hepatocyte growth factor (HGF) increases beta-cell proliferation and promotes revascularization of islets, while interleukin-1 receptor antagonist (hIL-1Ra) inhibits islet cell apoptosis.
methodsWe constructed Adv-hHGF-hIL-1Ra by cloning hHGF and hIL-1Ra coding sequences and polyA signal under separate CMV promoters in Adenoquick plasmid.
resultsThere was dose and time dependent expression of these genes after transduction of Adv-hHGF-hIL-1Ra into human islets. Compared to un-transduced islets, hHGF and hIL-1Ra gene expression at protein levels was more than 60 and 40 times higher at 1,000 MOI, respectively. Transduced islets were viable after incubation with the cocktail of TNF-alpha, IL-1beta and IFN-gamma, as evidenced by insulin release in response to glucose concentration. Co-expression of hHGF and hIL-1Ra led to significant decrease in caspase-3 induced by the cytokines. Compared to un-transduced islets, transduction of islets with Adv-hHGF-hIL-1Ra at 1,000 MOI prior to transplantation under the kidney capsules of streptozotocin-induced-diabetic NOD-SCID mice reduced blood glucose levels, and increased serum insulin and c-peptide levels.
conclusionsTransduction of islets with Adv-hHGF-hIL-1Ra efficiently expresses both growth factor and antiapoptotic genes, decreases caspase-3 and improves the outcome of islet transplantation.
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