Wound-healing factors secreted by epidermal keratinocytes and dermal fibroblasts in skin substitutes

Wound Repair Regen. 2007 Sep-Oct;15(5):708-17. doi: 10.1111/j.1524-475X.2007.00280.x.

Abstract

Full-skin substitutes, epidermal substitutes, and dermal substitutes are currently being used to heal deep burns and chronic ulcers. In this study, we investigated which wound-healing mediators are released from these constructs and whether keratinocyte-fibroblast interactions are involved. Autologous skin substitutes were constructed from human keratinocytes, fibroblasts, and acellular donor dermis. Full-thickness skin was used to represent an autograft. Secretion of wound-healing mediators was investigated by means of protein array, enzyme-linked immunosorbent assay, neutralizing antibodies, and conditioned culture supernatants. Full-skin substitutes and autografts produce high amounts of inflammatory/angiogenic mediators (IL-6, CCL2, CXCL1, CXCL8, and sST2). Epidermal and dermal substitutes produced less of these proteins. Epidermal-derived proinflammatory cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) were found to mediate synergistically the secretion of these wound-healing mediators (with the exception of sST2) from fibroblasts in dermal substitutes. The secretion of proinflammatory cytokines (IL-1alpha, TNF-alpha), chemokine/mitogen (CCL5) and angiogenic factor (vascular endothelial growth factor) by epidermal substitutes and tissue remodeling factors (tissue inhibitor of metalloproteinase-2, hepatocyte growth factor) by dermal substitutes was not influenced by keratinocyte-fibroblast interactions. The full-skin substitute has a greater potential to stimulate wound healing than epidermal or dermal substitutes. Both epidermal-derived IL-1alpha and TNF-alpha are required to trigger the release of dermal-derived inflammatory/angiogenic mediators from skin substitutes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Chemokine CCL5 / metabolism
  • Chemokine CXCL1 / metabolism
  • Coculture Techniques
  • Epidermal Cells*
  • Fibroblasts / physiology*
  • Humans
  • Interleukin-1 / physiology*
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Keratinocytes / metabolism
  • Keratinocytes / physiology*
  • Skin Transplantation / physiology
  • Skin, Artificial*
  • Transplantation, Autologous
  • Tumor Necrosis Factor-alpha / physiology*
  • Wound Healing / physiology*

Substances

  • Chemokine CCL5
  • Chemokine CXCL1
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha