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

(2018) DIABETOLOGIA. 61(8). p.1804-1810
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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 mu l [n = 7] in VEGF vs 0.0178 +/- 0.0021 mu l [n = 5] in no RNA [p < 0.01] vs 0.0129 +/- 0.0012 mu l [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.
Keywords
Cell therapy, Diabetes, Gene delivery, Graft revascularisation, Islet transplantation, Messenger RNA, Pancreatic beta cell, RNA delivery, VEGFA, BETA-CELL MASS, PANCREATIC-ISLETS, SHORT-TERM, TRANSPLANTATION, PROTECTS, THERAPY

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MLA
Staels, Willem et al. “Vegf-A mRNA Transfection as a Novel Approach to Improve Mouse and Human Islet Graft Revascularisation.” DIABETOLOGIA 61.8 (2018): 1804–1810. Print.
APA
Staels, W., Verdonck, Y., Heremans, Y., Leuckx, G., De Groef, S., Heirman, C., de Koning, E., et al. (2018). Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation. DIABETOLOGIA, 61(8), 1804–1810.
Chicago author-date
Staels, Willem, Yannick Verdonck, Yves Heremans, Gunter Leuckx, Sofie De Groef, Carlo Heirman, Eelco de Koning, et al. 2018. “Vegf-A mRNA Transfection as a Novel Approach to Improve Mouse and Human Islet Graft Revascularisation.” Diabetologia 61 (8): 1804–1810.
Chicago author-date (all authors)
Staels, Willem, Yannick Verdonck, Yves Heremans, Gunter Leuckx, Sofie De Groef, Carlo Heirman, Eelco de Koning, Conny Gysemans, Kris Thielemans, Luc Baeyens, Harry Heimberg, and Nico De Leu. 2018. “Vegf-A mRNA Transfection as a Novel Approach to Improve Mouse and Human Islet Graft Revascularisation.” Diabetologia 61 (8): 1804–1810.
Vancouver
1.
Staels W, Verdonck Y, Heremans Y, Leuckx G, De Groef S, Heirman C, et al. Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation. DIABETOLOGIA. 2018;61(8):1804–10.
IEEE
[1]
W. Staels et al., “Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation,” DIABETOLOGIA, vol. 61, no. 8, pp. 1804–1810, 2018.
@article{8566258,
  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 mu l [n = 7] in VEGF vs 0.0178 +/- 0.0021 mu l [n = 5] in no RNA [p < 0.01] vs 0.0129 +/- 0.0012 mu l [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.},
  author       = {Staels, Willem and Verdonck, Yannick and Heremans, Yves and Leuckx, Gunter and De Groef, Sofie and Heirman, Carlo and de Koning, Eelco and Gysemans, Conny and Thielemans, Kris and Baeyens, Luc and Heimberg, Harry and De Leu, Nico},
  issn         = {0012-186X},
  journal      = {DIABETOLOGIA},
  keywords     = {Cell therapy,Diabetes,Gene delivery,Graft revascularisation,Islet transplantation,Messenger RNA,Pancreatic beta cell,RNA delivery,VEGFA,BETA-CELL MASS,PANCREATIC-ISLETS,SHORT-TERM,TRANSPLANTATION,PROTECTS,THERAPY},
  language     = {eng},
  number       = {8},
  pages        = {1804--1810},
  title        = {Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation},
  url          = {http://dx.doi.org/10.1007/s00125-018-4646-7},
  volume       = {61},
  year         = {2018},
}

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