Impaired vascular remodeling after endothelial progenitor cell transplantation in MMP9-deficient mice suffering cortical cerebral ischemia

J Cereb Blood Flow Metab. 2015 Oct;35(10):1547-51. doi: 10.1038/jcbfm.2015.180. Epub 2015 Jul 29.

Abstract

Endothelial progenitor cells (EPCs) are being investigated for advanced therapies, and matrix metalloproteinase 9 (MMP9) has an important role in stroke recovery. Our aim was to determine whether tissue MMP9 influences the EPC-induced angiogenesis after ischemia. Wild-type (WT) and MMP9-deficient mice (MMP9/KO) were subjected to cerebral ischemia and treated with vehicle or outgrowth EPCs. After 3 weeks, we observed an increase in the peri-infarct vessel density in WT animals but not in MMP9/KO mice; no differences were found in the vehicle-treated groups. Our data suggest that tissue MMP9 has a crucial role in EPC-induced vascular remodeling after stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy
  • Cerebral Cortex / pathology*
  • Cerebral Infarction / pathology
  • Cerebral Infarction / physiopathology
  • Cerebral Veins / growth & development
  • Cerebral Veins / physiology*
  • DNA-Binding Proteins
  • Doublecortin Domain Proteins
  • Endothelial Progenitor Cells*
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 9 / deficiency
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / physiology*
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neuropeptides / genetics
  • Neuropeptides / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Stem Cell Transplantation / methods*
  • Stroke / therapy
  • Vascular Remodeling*

Substances

  • DNA-Binding Proteins
  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Neuropeptides
  • Nuclear Proteins
  • Matrix Metalloproteinase 9