Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing.
(2014) Molecular Therapy — Vol. 22, n° 4, p. 734-742 (2014)
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- Host defense peptides, in particular LL-37, are emerging as potential therapeutics for promoting wound healing and inhibiting bacterial growth. However, effective delivery of the LL-37 peptide remains limiting. We hypothesized that skin-targeted electroporation of a plasmid encoding hCAP-18/LL-37 would promote the healing of wounds. The plasmid was efficiently delivered to full-thickness skin wounds by electroporation and it induced expression of LL-37 in the epithelium. It significantly accelerated reepithelialization of nondiabetic and diabetic wounds and caused a significant VEGFa and interleukin (IL)-6 induction. IL-6 was involved in LL-37-mediated keratinocyte migration in vitro and IL-6 neutralizing antibodies delivered to mice were able to suppress the wound healing activity of the hCAP-18/LL-37 plasmid. In a hindlimb ischemia model, electroporation of the hCAP-18/LL-37 plasmid increased blood perfusion, reduced muscular atrophy, and upregulated the angiogenic chemokines VEGFa and SDF-1a, and their receptors VEGF-R and CXCR-4. These findings demonstrate that a localized gene therapy with LL-37 is a promising approach for the treatment of wounds.
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Steinstraesser, L., Lam, M. C., Jacobsen, F., Porporato, P., Chereddy, K. K., Becerikli, M., Stricker, I., Hancock, R. E., Lehnhardt, M., Sonveaux, P., Préat, V., & Vandermeulen, G. (2014). Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing. Molecular Therapy, 22(4), 734-742. https://doi.org/10.1038/mt.2013.258 (Original work published 2014)