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The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation
University of Skövde, Systems Biology Research Environment. University of Skövde, School of Bioscience. Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. (Translationell bioinformatik, Translational Bioinformatics)ORCID iD: 0000-0001-5945-817X
Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
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2024 (English)In: Cells, E-ISSN 2073-4409, Vol. 13, no 5, article id 414Article in journal (Refereed) Published
Abstract [en]

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.

Place, publisher, year, edition, pages
MDPI, 2024. Vol. 13, no 5, article id 414
Keywords [en]
angiogenesis, diabetes, diabetic foot ulcer, FGF1, revascularization, VEGF-A, wound healing, Animals, Diabetes Mellitus, Experimental, Diabetic Foot, Disease Models, Animal, Fibroblast Growth Factor 1, Humans, Mice, Neovascularization, Physiologic, Vascular Endothelial Growth Factor A, vasculotropin A, animal, disease model, experimental diabetes mellitus, human, metabolism, mouse, physiology
National Category
Endocrinology and Diabetes Cardiac and Cardiovascular Systems Surgery Clinical Science
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:his:diva-23666DOI: 10.3390/cells13050414ISI: 001182677000001PubMedID: 38474378Scopus ID: 2-s2.0-85187416799OAI: oai:DiVA.org:his-23666DiVA, id: diva2:1846121
Funder
Knowledge Foundation, 20200014
Note

 CC BY 4.0 DEED

© 2024 by the authors.

Correspondence Address: S. Tejedor; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 50, Sweden; email: sandra.tejedorgascon1@astrazeneca.com; K. Hansson; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 50, Sweden; email: kenny.m.hansson@astrazeneca.com

This research was partially funded by grants from the Swedish Knowledge Foundation, grant number 20200014.

Available from: 2024-03-21 Created: 2024-03-21 Last updated: 2024-04-15Bibliographically approved

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Tejedor, SandraDönnes, PierreSynnergren, Jane

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