Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing

Lars Steinstraesser, Martin C. Lam, Frank Jacobsen, Paolo E. Porporato, Kiran Kumar Chereddy, Mustafa Becerikli, Ingo Stricker, Robert Hancock, Marcus Lehnhardt, Pierre Sonveaux, Véronique Préat, Gaëlle Vandermeulen

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages734-742
Number of pages9
JournalMolecular Therapy
Volume22
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Steinstraesser, L., Lam, M. C., Jacobsen, F., Porporato, P. E., Chereddy, K. K., Becerikli, M., ... 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