Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation

Willem Staels, Yannick Verdonck, Yves Heremans, Gunter Leuckx, Sofie De Groef, Carlo Heirman, Eelco de Koning, Conny Gysemans, Kris Thielemans, Luc Baeyens, Harry Heimberg, Nico De Leu

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

AIMS/HYPOTHESIS: The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation 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 vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice.

RESULTS: At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA-transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean ± SEM: 0.118 ± 0.01 [n = 3] in Vegf-A mRNA transfected group (VEGF) vs 0.056 ± 0.01 [n = 3] in no RNA [p < 0.05] vs 0.063 ± 0.02 [n = 4] in Gfp mRNA transfected group (GFP) [p < 0.05]); EndoC-bH3 grafts (2.85- and 2.48-fold. respectively) (0.085 ± 0.02 [n = 4] in VEGF vs 0.030 ± 0.004 [n = 4] in no RNA [p < 0.05] vs 0.034 ± 0.01 [n = 5] in GFP [p < 0.05]); and human islet grafts (3.17- and 3.80-fold, respectively) (0.048 ± 0.013 [n = 3] in VEGF vs 0.015 ± 0.0051 [n = 4] in no RNA [p < 0.01] vs 0.013 ± 0.0046 [n = 4] in GFP [p < 0.01]). At day 30 post transplantation, human islet grafts maintained a vascularisation benefit (1.70- and 1.82-fold, respectively) (0.049 ± 0.0042 [n = 8] in VEGF vs 0.029 ± 0.0052 [n = 5] in no RNA [p < 0.05] vs 0.027 ± 0.0056 [n = 4] in GFP [p < 0.05]) and a higher beta cell volume (1.64- and 2.26-fold, respectively) (0.0292 ± 0.0032 μl [n = 7] in VEGF vs 0.0178 ± 0.0021 μl [n = 5] in no RNA [p < 0.01] vs 0.0129 ± 0.0012 μl [n = 4] in GFP [p < 0.001]).

CONCLUSIONS/INTERPRETATION: Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants.

Original languageEnglish
Pages (from-to)1804-1810
Number of pages7
JournalDiabetologia
Volume61
Issue number8
DOIs
Publication statusPublished - Aug 2018

Keywords

  • Animals
  • Cell Survival
  • Humans
  • Insulin/metabolism
  • Insulin-Secreting Cells/cytology
  • Islets of Langerhans/cytology
  • Islets of Langerhans Transplantation
  • Mice
  • Neovascularization, Physiologic
  • RNA, Messenger/genetics
  • Transfection
  • Vascular Endothelial Growth Factor A/genetics

Fingerprint

Dive into the research topics of 'Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation'. Together they form a unique fingerprint.

Cite this