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Original Articles
Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice
Junghae Ko, Haejung Jun, Hyesook Chung, Changshin Yoon, Taekyoon Kim, Minjeong Kwon, Soonhee Lee, Soojin Jung, Mikyung Kim, Jeong Hyun Park
Diabetes Metab J. 2011;35(3):226-235.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.226
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  • 38 Download
  • 20 Crossref
AbstractAbstract PDFPubReader   
Background

To accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds.

Methods

Streptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF828 and VEGF165 DNAs. Each gene was modified for increasing efficacy as FRM-EGF828 or minicircle VEGF165. The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group.

Results

In both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant.

Conclusion

Both non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different.

Citations

Citations to this article as recorded by  
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    Molecular Therapy - Nucleic Acids.2022; 29: 871.     CrossRef
  • Approaches to Modulate the Chronic Wound Environment Using Localized Nucleic Acid Delivery
    Adam G. Berger, Jonathan J. Chou, Paula T. Hammond
    Advances in Wound Care.2021; 10(9): 503.     CrossRef
  • Limited Treatment Options for Diabetic Wounds: Barriers to Clinical Translation Despite Therapeutic Success in Murine Models
    May Barakat, Luisa A. DiPietro, Lin Chen
    Advances in Wound Care.2021; 10(8): 436.     CrossRef
  • Minicircle‐based expression of vascular endothelial growth factor in mesenchymal stromal cells from diverse human tissues
    Joana Serra, Cláudia P. A. Alves, Joaquim M. S. Cabral, Gabriel A. Monteiro, Cláudia L. da Silva, Duarte Miguel F. Prazeres
    The Journal of Gene Medicine.2021;[Epub]     CrossRef
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  • β-Neoendorphin Enhances Wound Healing by Promoting Cell Migration in Keratinocyte
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    Molecules.2020; 25(20): 4640.     CrossRef
  • Orf Virus IL-10 and VEGF-E Act Synergistically to Enhance Healing of Cutaneous Wounds in Mice
    Lyn M. Wise, Gabriella S. Stuart, Nicola C. Jones, Stephen B. Fleming, Andrew A. Mercer
    Journal of Clinical Medicine.2020; 9(4): 1085.     CrossRef
  • Engineering of Human Mesenchymal Stem/Stromal Cells with Vascular Endothelial Growth Factor–Encoding Minicircles for AngiogenicEx VivoGene Therapy
    Joana Serra, Cláudia P.A. Alves, Liliana Brito, Gabriel A. Monteiro, Joaquim M.S. Cabral, Duarte Miguel F. Prazeres, Cláudia L. da Silva
    Human Gene Therapy.2019; 30(3): 316.     CrossRef
  • Therapeutic strategies for enhancing angiogenesis in wound healing
    Austin P. Veith, Kayla Henderson, Adrianne Spencer, Andrew D. Sligar, Aaron B. Baker
    Advanced Drug Delivery Reviews.2019; 146: 97.     CrossRef
  • Nanomedicines and gene therapy for the delivery of growth factors to improve perfusion and oxygenation in wound healing
    Céline M. Desmet, Véronique Préat, Bernard Gallez
    Advanced Drug Delivery Reviews.2018; 129: 262.     CrossRef
  • Electrospun Fibers as a Dressing Material for Drug and Biological Agent Delivery in Wound Healing Applications
    Mulugeta Gizaw, Jeffrey Thompson, Addison Faglie, Shih-Yu Lee, Pierre Neuenschwander, Shih-Feng Chou
    Bioengineering.2018; 5(1): 9.     CrossRef
  • Non-viral gene therapy: Gains and challenges of non-invasive administration methods
    Marianna Foldvari, Ding Wen Chen, Nafiseh Nafissi, Daniella Calderon, Lokesh Narsineni, Amirreza Rafiee
    Journal of Controlled Release.2016; 240: 165.     CrossRef
  • RETRACTED ARTICLE: Decellularized scaffolds containing hyaluronic acid and EGF for promoting the recovery of skin wounds
    Zhengzheng Wu, Yan Tang, Hongdou Fang, Zhongchun Su, Bin Xu, Yongliang Lin, Peng Zhang, Xing Wei
    Journal of Materials Science: Materials in Medicine.2015;[Epub]     CrossRef
  • Acute and chronic wound fluids inversely influence adipose‐derived stem cell function: molecular insights into impaired wound healing
    Paola Koenen, Timo A Spanholtz, Marc Maegele, Ewa Stürmer, Thomas Brockamp, Edmund Neugebauer, Oliver C Thamm
    International Wound Journal.2015; 12(1): 10.     CrossRef
  • Adipose‐derived stem cells and keratinocytes in a chronic wound cell culture model: the role of hydroxyectoine
    Oliver C Thamm, Panagiotis Theodorou, Ewa Stuermer, Max J Zinser, Edmund A Neugebauer, Paul C Fuchs, Paola Koenen
    International Wound Journal.2015; 12(4): 387.     CrossRef
  • Genetic and cellular techniques emerge as promising modalities for the treatment of diabetic foot syndrome
    Vladimir Iosifovich Konenkov, Vadim Valerievich Klimontov
    Diabetes mellitus.2014; 17(1): 63.     CrossRef
  • Analysis of blood flow and local expression of angiogenesis-associated growth factors in infected wounds treated with negative pressure wound therapy
    CHENG-YAN XIA, AI-XI YU, BAIWEN QI, MIN ZHOU, ZONG-HUAN LI, WEI-YANG WANG
    Molecular Medicine Reports.2014; 9(5): 1749.     CrossRef
  • Alteration of Skin Properties with Autologous Dermal Fibroblasts
    Rajesh Thangapazham, Thomas Darling, Jon Meyerle
    International Journal of Molecular Sciences.2014; 15(5): 8407.     CrossRef
  • Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice
    Han Chung Chong, Jeremy Soon Kiat Chan, Chi Qin Goh, Natalia V Gounko, Baiwen Luo, Xiaoling Wang, Selin Foo, Marcus Thien Chong Wong, Cleo Choong, Sander Kersten, Nguan Soon Tan
    Molecular Therapy.2014; 22(9): 1593.     CrossRef
  • Genome Editing of Mouse Fibroblasts by Homologous Recombination for Sustained Secretion of PDGF-B and Augmentation of Wound Healing
    Jenny C. Barker, Adam D. Barker, Jessica Bills, Jiying Huang, Mary Wight-Carter, Imelda Delgado, Debby L. Noble, Lily J. Huang, Matthew H. Porteus, Kathryn E. Davis
    Plastic and Reconstructive Surgery.2014; 134(3): 389e.     CrossRef
Comparison of Minicircle with Conventional Plasmid for the Non-viral Vascular Endothelial Growth Factor (VEGF) Gene Therapy.
Minjeong Kwon, Soonhee Lee, Heysook Chung, Changshin Yoon, Mikyung Kim, Jeonghyun Park
Korean Diabetes J. 2007;31(6):465-471.   Published online November 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.6.465
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  • 24 Download
AbstractAbstract PDF
BACKGROUND
Delayed wound healings in diabetic patients are related with the impairment of the expressions of various growth factors. Treatments using growth factors have been attempted on diabetic foot ulcer. VEGF (vascular endothelial growth factor) accelerates neo-angiogenesis on the early phase of the wound healing and exerts chemo-attractive effect for the other growth factors and cytokines. Non-viral gene transfer strategies are attractive tool for the gene therapy due to the safety and the versatility, but the low efficiency has been the serious problem. METHODS: We performed the VEGF gene therapy using reconstructed minicircle MINI-pbetaVEGF DNA with a polymeric carrier, polyethylenimine (PEI, 25 kDa) in HEK293, CHO, and NIH3T3 cell lines, and compared its efficiency with the conventional VEGF plasmid pbetaVEGF. RESULTS: The levels of expressed VEGF were higher in the groups using BPEI (branched PEI) as a gene carrier than naked plasmid transfer in all cell lines (P < 0.05). The minicircle MINI-pbetaVEGF DNA showed much higher VEGF expression than conventional plasmid pbetaVEGF (P < 0.05). CONCLUSION: Minicircle DNA MINI-pbetaVEGF showed much higher transfection efficiency than conventional plasmid pbetaVEGF. It might be used in actual human clinical trial due to its higher efficiency and possible safety for the treatment of diabetic foot ulcer.

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