circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models

Nat Commun. 2024 May 9;15(1):3904. doi: 10.1038/s41467-024-48284-3.

Abstract

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Diabetes Mellitus, Experimental*
  • Disease Models, Animal
  • Extracellular Vesicles* / chemistry
  • Fibroblasts* / drug effects
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Keratinocytes* / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Circular* / pharmacology
  • RNA, Circular* / therapeutic use
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Rats
  • Skin / drug effects
  • Wound Healing* / drug effects

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • Proto-Oncogene Proteins c-myc
  • RNA, Circular
  • RNA-Binding Proteins