IL-1β-Primed Mesenchymal Stromal Cells Improve Epidermal Substitute Engraftment and Wound Healing via Matrix Metalloproteinases and Transforming Growth Factor-β1

J Invest Dermatol. 2020 Mar;140(3):688-698.e21. doi: 10.1016/j.jid.2019.07.721. Epub 2019 Sep 9.

Abstract

Since the 1980s, deep and extensive skin wounds and burns are treated with autologous split-thickness skin grafts, or cultured epidermal autografts, when donor sites are limited. However, the clinical use of cultured epidermal autografts often remains unsatisfactory because of poor engraftment rates, altered wound healing, and reduced skin functionality. In the past few decades, mesenchymal stromal cells (MSCs) have raised much attention because of their anti-inflammatory, protrophic, and pro-remodeling capacities. More specifically, gingival MSCs have been shown to possess enhanced wound healing properties compared with other tissue sources. Growing evidence also indicates that MSC priming could potentiate therapeutic effects in diverse in vitro and in vivo models of skin trauma. In this study, we found that IL-1β-primed gingival MSCs promoted cell migration, dermal-epidermal junction formation, and inflammation reduction in vitro, as well as improved epidermal substitute engraftment in vivo. IL-1β-primed gingival MSCs had different secretory profiles from naive gingival MSCs, characterized by an overexpression of transforming growth factor-β and matrix metalloproteinase (MMP) pathway agonists. Eventually, MMP-1, MMP-9, and transforming growth factor-β1 appeared to be critically involved in IL-1β-primed gingival MSC mechanisms of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Disease Models, Animal
  • Fibroblasts
  • Gingiva / cytology
  • Healthy Volunteers
  • Humans
  • Interleukin-1beta / metabolism*
  • Keratinocytes
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Primary Cell Culture / methods
  • Recombinant Proteins / metabolism
  • Skin / injuries*
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing / physiology*

Substances

  • Culture Media, Conditioned
  • IL1B protein, human
  • Interleukin-1beta
  • Recombinant Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP1 protein, human
  • Matrix Metalloproteinase 1