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

Autor: Harry Heimberg, Gunter Leuckx, Eelco J.P. de Koning, Yves Heremans, Yannick Verdonck, Carlo Heirman, Nico De Leu, Willem Staels, Kris Thielemans, Sofie De Groef, Luc Baeyens, Conny Gysemans
Přispěvatelé: Pathology/molecular and cellular medicine, Beta Cell Neogenesis, Faculty of Medicine and Pharmacy, Faculty of Sciences and Bioengineering Sciences, Laboratory of Molecullar and Cellular Therapy, Basic (bio-) Medical Sciences, Physiology, Immunomodulation in Chronic Inflammatory Diseases, Hematology, Medical Oncology, Pathologic Biochemistry and Physiology, Clinical sciences, Internal Medicine, Hubrecht Institute for Developmental Biology and Stem Cell Research
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Vascular Endothelial Growth Factor A
RNA
Messenger/genetics

0301 basic medicine
medicine.medical_treatment
VEGF receptors
Endocrinology
Diabetes and Metabolism

Islets of Langerhans Transplantation
Cell therapy
Insulin-Secreting Cells/cytology
0302 clinical medicine
Insulin-Secreting Cells
Insulin
Medicine
Mrna transfection
Gene delivery
Islet transplantation
Pancreatic beta cell
geography.geographical_feature_category
biology
Messenger RNA
Diabetes
Transfection
Islet
3. Good health
Islets of Langerhans/cytology
Vascular endothelial growth factor A
Beta cell
Graft revascularisation
VEGFA
mice
Insulin/metabolism
Cell Survival
Neovascularization
Physiologic

RNA delivery
030209 endocrinology & metabolism
Revascularization
Viral vector
Vascular Endothelial Growth Factor A/genetics
Andrology
Islets of Langerhans
03 medical and health sciences
Internal Medicine
Humans
Animals
RNA
Messenger

Physiologic
Neovascularization
geography
business.industry
Transplantation
030104 developmental biology
Cancer research
biology.protein
RNA
Messenger/genetics
business
Zdroj: Diabetologia
Diabetologia, 61(8), 1804-1810. Springer Verlag GmbH
Diabetologia, 61(8), 1804-1810
ISSN: 0012-186X
DOI: 10.1007/s00125-018-4646-7
Popis: 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
Databáze: OpenAIRE