Aims/hypothesis: The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularization to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment.
Methods: Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor Vegf-A before transplantation under the kidney capsule in mouse.
Results: At day 7 posttransplantation (PT), revascularization of Vegf-A mRNA transfected grafts was significantly higher compared to respectively non-transfected or Gfp mRNA transfected controls in both mouse islet grafts (1.87- and 2.11-fold), EndoC-bH3 (2.85- and 2.48-fold), and human islet grafts (3.17- and 3.80-fold). At day 30 PT, human islet grafts maintained a vascularization benefit (1.70- and 1.82-fold) and a higher beta cell volume (1.64- and 2.26-fold).
Conclusions/interpretation: Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants.
19 - 20 Oct 2018
Belgian Endocrine Society