Adenovirus-mediated VEGF165 gene transfer enhances wound healing by promoting angiogenesis in CD1 diabetic mice

Peppe, Simona Romano Di; Mangoni, Antonella; Zambruno, Giovanna; Spinetti, Gaia; Melillo, G; Napolitano, Monica; Capogrossi, Maurizio C.

doi:10.1038/sj.gt.3301798

Cited by 109 publications

(49 citation statements)

References 42 publications

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“…By looking at the capillary number in the granulation tissues, more capillaries were found in the RR extract group on day 8; this was further supported by the observation of enhancement in the expression of VEGF from epidermal cells earlier on from day 4. VEGF is a potent growth factor for angiogenesis and essential in wound healing (Leung et al, 1989;Brown et al, 1992;Altavilla et al, 2001;Elcin et al, 2001;Romano Di Peppe et al, 2002;Galeano et al, 2003;Galiano et al, 2004). Our findings demonstrated that epidermis was mainly responsible for the VEGF expression which is consistent with the findings of other research groups (Brown et al, 1992).…”

Section: Discussionsupporting

confidence: 95%

“…Immunohistochemical methods were also used to determine the release of vascular endothelial growth factor (VEGF) in the ulcer area. VEGF is a proangiogenic cytokine widely used to assess the formation of new blood vessels during wound repairs (Leung et al, 1989;Brown et al, 1992;Altavilla et al, 2001;Elcin et al, 2001;Romano Di Peppe et al, 2002;Galeano et al, 2003;Galiano et al, 2004).…”

Section: Angiogenesis Studymentioning

confidence: 99%

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Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer

Lau

Lam

Lau

et al. 2009

Journal of Ethnopharmacology

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Section: Discussionsupporting

confidence: 95%

Section: Angiogenesis Studymentioning

confidence: 99%

Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer

Lau

Lam

Lau

et al. 2009

Journal of Ethnopharmacology

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“…This finding was unexpected considering the many reports of delayed healing of excisional skin wounds in STZ-induced diabetes in mice [13,14,16,32] and rats [15]. Our negative results suggest differences in repair mechanisms between PUs and surgical skin wounds.…”

Section: Discussioncontrasting

confidence: 53%

Pressure Ulcers: Description of a New Model and Use of Mesenchymal Stem Cells for Repair

Garza-Rodea

Knaän‐Shanzer

Bekkum³

2011

Dermatology

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Background: Pressure ulcers (PUs) still represent a heavy burden on many patients and nursing institutions. Our understanding of the pathophysiology and development of new treatments are hampered by the scarcity of suitable animal models. Objective: Evaluation of the translational value of an easily accessible mouse model. Methods: PUs were induced by application of magnetic devices on the dorsal skin of mice, which causes localized ischemia. The extent of the lesions and healing rate were quantified. Variations in ischemic exposure time were compared in hairless and normal mice. A detailed histological analysis of regeneration is presented. The influence of streptozotocin-induced diabetes, skin X-irradiation and treatment of the ulcers with human mesenchymal stem cells (MSCs) was investigated using immunodeficient NOD/SCID mice. Results: Ulcers induced by this form of ischemia have many features in common with decubitus ulcers in humans. No difference between hairy and hairless mice was observed in the rate of healing of the PUs. Unexpectedly, healing was not delayed in diabetic mice, but skin X-irradiation prior to ischemia resulted in a doubling of the time to complete closure of the PUs, and delayed repair of the dermis and panniculus carnosus muscle. Intradermal transplantation of human MSCs did not accelerate healing. The grafted MSCs were short-lived and only marginally participated in regeneration by differentiating into tissue-specific cells. Conclusion: The results emphasize the difference in the characteristics of PUs as compared to surgical wounds. This experimental model is recommended for preclinical research on decubitus ulcers because of its mechanistic similarity with clinical PUs and its simplicity.

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“…In addition, other cellular dysfunctions including inefficient reparative angiogenesis [26], abnormal control of cell survival [27] and impaired host signaling to the site of injury contribute to the delayed healing of diabetic wounds. Such impaired functions have been reported in cells derived from diabetic db/db mice [28].…”

Section: Discussionmentioning

confidence: 99%

Amniotic Mesenchymal Stem Cells Enhance Wound Healing in Diabetic NOD/SCID Mice through High Angiogenic and Engraftment Capabilities

et al. 2012

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Although human amniotic mesenchymal stem cells (AMMs) have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs) and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM) significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities.

show abstract

Adenovirus-mediated VEGF165 gene transfer enhances wound healing by promoting angiogenesis in CD1 diabetic mice

Cited by 109 publications

References 42 publications

Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer

Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer

Pressure Ulcers: Description of a New Model and Use of Mesenchymal Stem Cells for Repair

Amniotic Mesenchymal Stem Cells Enhance Wound Healing in Diabetic NOD/SCID Mice through High Angiogenic and Engraftment Capabilities

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