ArticleJournal of biomedical science2009
Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice.
Article in Journal of biomedical science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Emerging Roles of Metallothioneins in Human Pathophysiology: A Review.Health science reports · 2025Article
- Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Context-dependent effects of CCN2 on β-cell mass expansion and indicators of cell stress in the setting of acute and chronic stress.American journal of physiology. Endocrinology and metabolism · 2023Article
- Hydrogen peroxide detoxification through the peroxiredoxin/thioredoxin antioxidant system: A look at the pancreatic β-cell oxidant defense.Vitamins and hormones · 2023Article
- IL-10 lentivirus-laden hydrogel tubes increase spinal progenitor survival and neuronal differentiation after spinal cord injury.Biotechnology and bioengineering · 2021Article
- Synergistic Effect of the Long-Term Overexpression of Bcl-2 and BDNF Lentiviral in Cell Protecting against Death and Generating TH Positive and CHAT Positive Cells from MSC.International journal of molecular sciences · 2021Article
- Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and Above Metal Homeostasis and Antioxidant Response.Biology · 2021Review
- The Role of Thioredoxin/Peroxiredoxin in the β-Cell Defense Against Oxidative Damage.Frontiers in endocrinology · 2021Review
- Early Predictors in the Onset of Type 2 Diabetes at Different Fasting Blood Glucose Levels.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Paracrine regulation and improvement of β-cell function by thioredoxin.Redox biology · 2020Article
- Redox-Dependent Inflammation in Islet Transplantation Rejection.Frontiers in endocrinology · 2018Review
- A Simple High Efficiency Intra-Islet Transduction Protocol Using Lentiviral Vectors.Current gene therapy · 2015Article
- Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic β-cell.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling.Antioxidants & redox signaling · 2013Review
- The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells.Cell death & disease · 2013Article
- Thioredoxin-1 attenuates early graft loss after intraportal islet transplantation in mice.PloS one · 2013Article
- Gene delivery to pancreatic exocrine cells in vivo and in vitro.BMC biotechnology · 2012Article
- Genetically engineered islets and alternative sources of insulin-producing cells for treating autoimmune diabetes: quo vadis?International journal of endocrinology · 2012Article
- Two tales of antioxidant enzymes on β cells and diabetes.Antioxidants & redox signaling · 2011Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledPancreatic islet transplantation is considered an appropriate treatment to achieve insulin independence in type I diabetic patients. However, islet isolation and transplantation-induced oxidative stress and autoimmune-mediated destruction are still the major obstacles to the long-term survival of graft islets in this potential therapy. To protect islet grafts from inflammatory damage and prolong their survival, we transduced islets with an antioxidative gene thioredoxin (TRX) using a lentiviral vector before transplantation. We hypothesized that the overexpression of TRX in islets would prolong islet graft survival when transplanted into diabetic non-obese diabetic (NOD) mice.
methodsIslets were isolated from NOD mice and transduced with lentivirus carrying TRX (Lt-TRX) or enhanced green fluorescence protein (Lt-eGFP), respectively. Transduced islets were transplanted under the left kidney capsule of female diabetic NOD mice, and blood glucose concentration was monitored daily after transplantation. The histology of the islet graft was assessed at the end of the study. The protective effect of TRX on islets was investigated.
resultsThe lentiviral vector effectively transduced islets without altering the glucose-stimulating insulin-secretory function of islets. Overexpression of TRX in islets reduced hydrogen peroxide-induced cytotoxicity in vitro. After transplantation into diabetic NOD mice, euglycemia was maintained for significantly longer in Lt-TRX-transduced islets than in Lt-eGFP-transduced islets; the mean graft survival was 18 vs. 6.5 days (n = 9 and 10, respectively, p < 0.05).
conclusionWe successfully transduced the TRX gene into islets and demonstrated that these genetically modified grafts are resistant to inflammatory insult and survived longer in diabetic recipients. Our results further support the concept that the reactive oxygen species (ROS) scavenger and antiapoptotic functions of TRX are critical to islet survival after transplantation.
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