Mesenchymal stem cells improve wound healing in vivo via early activation of matrix metalloproteinase-9 and vascular endothelial growth factor

J Korean Med Sci. 2011 Jun;26(6):726-33. doi: 10.3346/jkms.2011.26.6.726. Epub 2011 May 18.

Abstract

We investigated the effects of mesenchymal stem cells (MSCs) on wound healing using a three-dimensional (3D) collagen gel scaffold. Three circular full-thickness skin defects were created on the back of Sprague-Dawley rats. One site was covered with a 3D collagen gel containing 2 × 10(6) MSCs (MSCs+/3D collagen+). Another site was replaced with a 3D collagen gel without MSCs and the third site was left empty. The wound size was significantly reduced in the MSCs+/3D collagen+ sites. MSCs+/3D collagen+ sites exhibited the most neovascularization. FISH showed that Y-chromosome possessing cells were found within the dermis of MSCs+/3D collagen+ sites. Gelatin zymography revealed that the most intense expression of MMP-9 was detected early in the MSCs+/3D collagen+ sites. Our results indicate that MSCs upregulate the early expression of MMP-9 which induces the early mobilization of VEGF. Thus, MSCs appear to accelerate significantly wound healing via early activation of MMP-9 and VEGF.

Keywords: Mesenchymal Stem Cells; Wound Healing.

MeSH terms

  • Animals
  • Collagen / pharmacology
  • Female
  • Immunohistochemistry
  • Matrix Metalloproteinase 9 / metabolism*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Neovascularization, Physiologic
  • Rats
  • Rats, Sprague-Dawley
  • Skin / pathology
  • Vascular Endothelial Growth Factor A / metabolism*
  • Wound Healing*

Substances

  • Vascular Endothelial Growth Factor A
  • Collagen
  • Matrix Metalloproteinase 9