Enhanced adipose-derived stem cells with IGF-1-modified mRNA promote wound healing following corneal injury

Mol Ther. 2023 Aug 2;31(8):2454-2471. doi: 10.1016/j.ymthe.2023.05.002. Epub 2023 May 10.


The cornea serves as an important barrier structure to the eyeball and is vulnerable to injuries, which may lead to scarring and blindness if not treated promptly. To explore an effective treatment that could achieve multi-dimensional repair of the injured cornea, the study herein innovatively combined modified mRNA (modRNA) technologies with adipose-derived mesenchymal stem cells (ADSCs) therapy, and applied IGF-1 modRNA (modIGF1)-engineered ADSCs (ADSCmodIGF1) to alkali-burned corneas in mice. The therapeutic results showed that ADSCmodIGF1 treatment could achieve the most extensive recovery of corneal morphology and function when compared not only with simple ADSCs but also IGF-1 protein eyedrops, which was reflected by the healing of corneal epithelium and limbus, the inhibition of corneal stromal fibrosis, angiogenesis and lymphangiogenesis, and also the repair of corneal nerves. In vitro experiments further proved that ADSCmodIGF1 could more significantly promote the activity of trigeminal ganglion cells and maintain the stemness of limbal stem cells than simple ADSCs, which were also essential for reconstructing corneal homeostasis. Through a combinatorial treatment regimen of cell-based therapy with mRNA technology, this study highlighted comprehensive repair in the damaged cornea and showed the outstanding application prospect in the treatment of corneal injury.

Keywords: IGF1-modified mRNA; adipose-derived mesenchymal stem cells; corneal alkali burn; corneal neovascularization; corneal nerves; corneal wound healing; limbal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue
  • Animals
  • Cornea
  • Corneal Diseases*
  • Corneal Injuries* / genetics
  • Corneal Injuries* / metabolism
  • Corneal Injuries* / therapy
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / pharmacology
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Wound Healing / genetics


  • Insulin-Like Growth Factor I