Effective modulation of transforming growth factor-β1 expression through engineered microRNA-based plasmid-loaded nanospheres

Cytotherapy. 2015 Mar;17(3):320-9. doi: 10.1016/j.jcyt.2014.09.004. Epub 2014 Oct 24.

Abstract

Background aims: Sustained gene delivery could be particularly necessary in modulating gene expression in healing intrasynovial tendons and may be a promising approach for preventing adhesions.

Methods: Polylactic-co-glycolic acid nanospheres were prepared and were then incorporated with plasmids expressing enhanced green fluorescence protein and miRNA for inhibiting the transforming growth factor-β1 gene expression.

Results: We demonstrated that cultured tenocytes could be effectively transfected by means of nanosphere/plasmid. The expression of transforming growth factor-β1 is significantly downregulated in healing chicken flexor tendon treated with nanosphere/plasmid. Histology analysis did not demonstrate any significant inflammation or necrosis in tendons injected with nanosphere/plasmid after surgery.

Conclusions: Nanosphere/plasmid may be a promising non-viral vector for gene therapy of the injured flexor tendon.

Keywords: flexor tendon; gene delivery; nanosphere; tissue reaction; transfection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chickens
  • Gene Expression
  • Genetic Therapy / methods*
  • Lactic Acid / chemistry
  • MicroRNAs / genetics*
  • Nanospheres / chemistry*
  • Plasmids / genetics*
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tendon Injuries / therapy*
  • Tendons / cytology
  • Transfection
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / genetics*
  • Wound Healing / genetics*

Substances

  • MicroRNAs
  • Transforming Growth Factor beta1
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid