Transfection with aFGF cDNA Improves Wound Healing

Abstract

Somatic gene therapy is a potentially useful strategy for the delivery of growth factors or cytokines to enhance wound healing. Experimental excisional and incisional wounds in impaired-healing diabetic mice (db/db) were treated with aFGF and with a plasmid coding for aFGF. A eukaryotic expression plasmid composed of the Hst signal peptide sequence in-frame with the human aFGF sequence was used. Transfection of tissues was accomplished either by direct plasmid uptake or by uptake facilitated with cationic liposomes. The results show that the closure of excisional wounds was significantly accelerated (p < 0.05) by topical application of human recombinant aFGF or by transfection with the aFGF plasmid but not by vehicle or control plasmid not containing the aFGF sequence. In incisional wounds, aFGF or transfection with the plasmid significantly increased the wound-breaking strength compared to their corresponding controls (p < 0.05). Quantitative histology of the plasmid-treated incisional wound sections revealed improved wound quality. The transcription of mRNA from human aFGF cDNA in the incisional wound tissue extracts was confirmed by RT-PCR, and the expressed aFGF was detected by immune dot blot and immunohistochemistry assays. The transfection was a transient process with a peak at 9 d in db/+ (littermates of the diabetic mice) incisional wounds, at 36 d in db/db incisional wounds, and at 27 d in db/db excisional wounds. Cells transfected with human aFGF occupied up to 6.4% of the transectional area in the wound sites. Thus, aFGF gene delivery resulted in both gene expression and a functional improvement in healing.

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

“…[38][39][40] VEGF gene transfer has been shown to enhance angiogenesis in animal models of hindlimb and cardiac ischemia and under these experimental conditions, it improves blood flow to the ischemic tissues. 25,36,41 In the present study VEGF 165 gene transfer, in the absence of experimentally induced ischemia, significantly improved wound healing in diabetic animals.…”

Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene

“…3 However, in acute dermal and epidermal wounds liposomal gene transfer of genes coding for growth factors was shown to be effective in improving dermal and epidermal regeneration. [4][5][6] Therefore, we used the physiologic cascade of wound healing as a model to investigate the effect of nonviral liposomal gene transfer. Wound healing is a dynamic interactive and complex process involving soluble mediators, blood cells, extracellular matrix and parenchymal cells.…”

Efficient gene transfer into human keratinocytes with recombinant adeno-associated virus vectors

“…Skin-directed gene transfer might be used for the treatment of a variety of skin diseases, [4][5][6][7][8] including acquired disorders such as cancer, burns or chronic non-healing wounds, [9][10][11] or inherited diseases such as epidermolysis bullosa, ichthyosis and xeroderma pigmentosum. [12][13][14][15][16] Moreover, systemic diseases such as adenosine deaminase deficiency, hemophilia A or B, and renal anemia might also be treated by transfer of a relevant therapeutic gene into the skin.…”