miR-21 modification enhances the performance of adipose tissue-derived mesenchymal stem cells for counteracting urethral stricture formation

J Cell Mol Med. 2018 Nov;22(11):5607-5616. doi: 10.1111/jcmm.13834. Epub 2018 Sep 4.

Abstract

The treatment of complicated long segment strictures remains to a challenge, and the substitution urethroplasty treatment is often accompanied by subsequent tissue fibrosis and secondary stricture formation. In situ injection of human adipose tissue-derived stem cells (hADSC) could potential be applied for prevention of urethral fibrosis, but the cells transplantation alone may be insufficient because of the complicated histopathological micro-environmental changes in the injury site. This study investigated whether miR-21 modification can improve the therapeutic efficacy of ADSCs against urethral fibrosis to limit urethral stricture recurrence. MiR-21-modified ADSCs (miR-21) were constructed via lentivirus-mediated transfer of pre-miR-21 and GFP reporter gene. In vitro results suggested that miR-21 modification can increase the angiogenesis genes expression of ADSCs and enhance its anti-oxidative effects against reactive oxygen species (ROS) damage. In vivo results showed that miR-21 modification contributes to increased urodynamic parameters and better formation of the epithelium and the muscle layer as compared to ADSCs transplantation alone groups. The results demonstrated that miR-21 modification in ADSCs could improve urethral wound healing microenvironment, enhance stem cell survival through ROS scavenging and promote the neovascularization via regulating angiogenic genes expression, which eventually increase the ADSCs' therapeutic potential for urethral wound healing.

Keywords: ADSCs; miR-21 modification; urethral stricture; wound healing.

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Epithelium / metabolism
  • Epithelium / pathology
  • Fibrosis / chemically induced
  • Fibrosis / genetics
  • Fibrosis / pathology
  • Fibrosis / therapy*
  • Gene Expression Regulation, Developmental / genetics
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / toxicity
  • Lentivirus / genetics
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / administration & dosage
  • MicroRNAs / genetics*
  • Muscles / cytology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Stem Cell Niche / genetics
  • Urethra / growth & development
  • Urethra / pathology
  • Urethral Stricture / genetics
  • Urethral Stricture / pathology
  • Urethral Stricture / therapy
  • Wound Healing / genetics

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • Hydrogen Peroxide