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Updated: Jul 18, 2026
Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
Beta-cell sparing in transplanted islets by vascular endothelial growth factor
J Stagner1, S Mokshagundam, K Wyler
1VA Medical Center, Louisville, Kentucky 40206, USA. john.stagner@med.va.gov
Abstract:
We have reported that vascular endothelial growth factor (VEGF) promotes the revascularization of transplanted islets, thereby reducing the initial number required to prevent diabetes. The present study was undertaken to assess other mechanisms of beta-cell sparing by VEGF. For in vitro studies, islets were cultured for 14 days with versus without 20 ng/mL VEGF. Viability, necrosis, and apoptosis were examined by specific staining (Alcein AM, propidium iodide, and annexin/phosphatidylserine). The effects of VEGF on islets were also examined in a proteomic study. In vivo streptozotocin-treated diabetic Lewis rats received 1000 Lewis or Sprague-Dawley islets beneath the renal capsule. Oxygen levels at the transplant site were monitored by a Clark-type oxygen electrode. Fasting blood glucose served as an indicator of islet survival and function. VEGF enhanced oxygen levels at the transplant site. Syngeneic recipients were euglycemic for over 6 months, whereas control islets failed within 30 to 60 days. VEGF prevented allograft rejection for over 14 days, whereas controls were rejected within 6 to 7 days. Immunostaining suggested that VEGF inhibited the presentation of MHC II antigen and promoted islet survival by the inhibition of necrosis and apoptosis. Our proteomic study suggested VEGF preserved systems required for cellular preservation (heat shock proteins) and insulin secretion. VEGF promotes the preservation of isolated and transplanted islets by a variety of mechanisms, including enhanced oxygenation and inhibition of immune rejection, necrosis, and apoptosis. The provision of exogenous VEGF may be a useful adjunct to islet transplantation.
Insights
Vascular endothelial growth factor (VEGF) enhances transplanted islet survival by improving oxygenation and reducing immune rejection, necrosis, and apoptosis. This promotes long-term diabetes prevention and islet preservation.
Area of Science:
- * Regenerative Medicine
- * Immunology
- * Endocrinology
Background:
- * Vascular Endothelial Growth Factor (VEGF) is known to promote revascularization of transplanted islets, reducing the number needed for diabetes prevention.
- * Further investigation into other beta-cell sparing mechanisms of VEGF is warranted.
Purpose of the Study:
- * To assess additional mechanisms by which VEGF spares beta-cells in islet transplantation.
- * To evaluate the effects of VEGF on islet viability, necrosis, and apoptosis in vitro and in vivo.
- * To examine the impact of VEGF on islet oxygenation, immune rejection, and overall function post-transplantation.
Main Methods:
- * In vitro: Islets cultured with/without VEGF (20 ng/mL) for 14 days; assessed viability, necrosis, apoptosis using specific stains.
- * Proteomic analysis of VEGF-treated islets.
- * In vivo: Streptozotocin-diabetic Lewis rats received syngeneic or allogeneic islets under the renal capsule.
- * Monitored oxygen levels at transplant site and fasting blood glucose.
- * Assessed allograft rejection and performed immunostaining for MHC II antigen.
Main Results:
- * VEGF significantly enhanced oxygen levels at the transplant site.
- * Syngeneic islet grafts in VEGF-treated recipients remained functional for over 6 months; controls failed within 30-60 days.
- * VEGF delayed allograft rejection by over 14 days compared to 6-7 days for controls.
- * VEGF inhibited MHC II antigen presentation, necrosis, and apoptosis, preserving islet cells.
- * Proteomic data indicated VEGF preserved heat shock proteins and insulin secretion systems.
Conclusions:
- * VEGF promotes isolated and transplanted islet preservation through multiple mechanisms.
- * Enhanced oxygenation and inhibition of immune rejection, necrosis, and apoptosis are key effects.
- * Exogenous VEGF shows potential as an adjunct therapy for islet transplantation to improve outcomes.
