Combination of chemically modified SDF-1α mRNA and small skin improves wound healing in diabetic rats with full-thickness skin defects

Cell Prolif. 2022 Dec;55(12):e13318. doi: 10.1111/cpr.13318. Epub 2022 Aug 6.

Abstract

Objectives: Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1α modRNA.

Materials and methods: The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed.

Results: The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro.

Conclusions: This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.

MeSH terms

  • Animals
  • Chemokine CXCL12* / genetics
  • Chemokine CXCL12* / pharmacology
  • Diabetes Mellitus, Experimental* / pathology
  • Diabetes Mellitus, Experimental* / therapy
  • Neovascularization, Physiologic
  • RNA, Messenger / genetics
  • Rats
  • Skin / pathology
  • Wound Healing

Substances

  • Chemokine CXCL12
  • RNA, Messenger