Nanoparticles prepared from porcine cells support the healing of cutaneous inflammation in mice and wound re-epithelialization in human skin

Exp Dermatol. 2017 Dec;26(12):1199-1206. doi: 10.1111/exd.13450. Epub 2017 Nov 7.

Abstract

Previous reports have demonstrated that cell-derived nanoparticles (CDNPs) composed of bovine or porcine protein complexes exerted therapeutic effects against viral infections and cancer in mice and humans. Based on these observations, we asked whether CDNPs would improve inflammatory skin disorders. To address this, we utilized two distinct mouse models of cutaneous inflammation: the autoimmune skin-blistering disease epidermolysis bullosa acquisita (EBA) as an example of an autoantibody-induced cutaneous inflammation, and Leishmania major (L. major) infection as an example of a pathogen-induced cutaneous inflammation. In both models, we observed that CDNPs increased mRNA expression of the Th2 cytokine IL-4. Clinically, CDNPs decreased inflammation due to EBA and increased L. major-specific IgG1 levels without major effects on infected skin lesions. In addition, CDNPs supported the growth of keratinocytes in human skin cultures. In vitro studies revealed that CDNPs were taken up predominantly by macrophages, leading to a shift towards the expression of anti-inflammatory cytokine genes. Altogether, our data demonstrate that treatment with porcine CDNPs may be a new therapeutic option for the control of autoimmune-mediated inflammatory skin disorders.

Keywords: autoimmune skin-blistering disease; therapy; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Differentiation
  • Cell-Derived Microparticles / transplantation*
  • Epidermolysis Bullosa Acquisita / immunology
  • Epidermolysis Bullosa Acquisita / therapy*
  • Female
  • Humans
  • Interleukin-4 / metabolism
  • Leishmania major
  • Leishmaniasis, Cutaneous / immunology
  • Leishmaniasis, Cutaneous / therapy*
  • Lymph Nodes / metabolism
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Re-Epithelialization*
  • Swine
  • Th2 Cells / physiology*
  • Young Adult

Substances

  • Interleukin-4