Endocrine Abstracts (2018) 57 008 | DOI: 10.1530/endoabs.57.008

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

Staels Willem1,2, Verdonck Yannick1, Heremans Yves1, Leuckx Gunter1, De Groef Sofie1, Heirman Carlo3, de Koning Eelco4, Gysemans Conny5, Thielemans Kris3, Baeyens Luc1, Heimberg Harry1 & De Leu Nico1,6,7

1Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Brussels, Belgium; 2Department of Paediatrics, Division of Paediatric Endocrinology, Ghent University, Ghent, Belgium; 3Laboratory of Molecular and Cellular Therapy (LMCT), Vrije Universiteit Brussel, Brussels, Belgium; 4Division of Endocrinology, Department of Medicine, LUMC, Leiden, The Netherlands; 5Laboratory of Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium; 6Department of Endocrinology, UZ Brussel, Brussels, Belgium; 7Department of Endocrinology, ASZ Aalst, Aalst, Belgium.

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.