Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice

Abstract

BackgroundTo 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.MethodsStreptozotocin 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.ResultsIn 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.ConclusionBoth 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.

Analysis of blood flow and local expression of angiogenesis-associated growth factors in infected wounds treated with negative pressure wound therapy

“…In addition, the angiogenesis-associated growth factors were not individually involved in angiogenesis, but interacted with and activated each other to promote angiogenesis. For example, in a study by Ko et al (40), VEGF enhanced neoangiogenesis, however, this was not effective on the maturation of organized reepithelization. The neoangiogenesis induced by EGF was not dominant, but did enhance the maturation of organized reepithelization.…”

Orf Virus IL-10 and VEGF-E Act Synergistically to Enhance Healing of Cutaneous Wounds in Mice

“…To our knowledge, no other combination wound healing therapies involving a growth factor and anti-inflammatory have been investigated. Others have explored the dual delivery of VEGF-A with either PDGF-β, fibroblast growth factor-4, insulin growth factor-1, keratinocyte growth factor, epidermal growth factor, angiopoietin-1 or bone morphogenic protein-2 on the healing of cutaneous wounds, hind-limb ischemia and bone defects [78][79][80][81][82][83]. The impact of a fusion between IL-10 and IL-4 has also been explored in the treatment of neuro-inflammatory pain [84].…”

Gene Therapy for Skin Diseases

“…Administration of minicircle-VEGF165 followed by insonication at 1 MHz showed reasonable wound closure and restored diabetic wound microarchitectures to their normal state (Yoon et al 2009). Ko et al (2011) compared EGF and VEGF gene therapy techniques in a diabetic mouse model using a minigene to deliver VEGF and a plasmid to deliver EGF. Both groups had accelerated wound healing when compared with control diabetic mice.…”