Tumor tissue derived extracellular vesicles promote diabetic wound healing

J Diabetes Complications. 2023 May;37(5):108435. doi: 10.1016/j.jdiacomp.2023.108435. Epub 2023 Feb 20.

Abstract

The diabetic wound nowadays remains a major public health challenge, which is characterized by overproduced reactive oxygen species (ROS). However, the current therapy for diabetic wounds is limited for reliable data in the general application. The growth of tumors has been revealed to share parallels with wound healing. Extracellular vesicles (EVs) derived from breast cancer have been reported to promote cell proliferation, migration and angiogenesis. The tumor tissue-derived EVs (tTi-EVs) of breast cancer performance a feature inheritance from original tissue and might accelerate the diabetic wound healing. We wonder whether the tumor-derived EVs are able to accelerate diabetic wound healing. In this study, tTi-EVs were extracted from breast cancer tissue via ultracentrifugation and size exclusion. Subsequently, tTi-EVs reversed the H2O2-induced inhibition of fibroblast proliferation and migration. Moreover, tTi-EVs significantly accelerated wound closure, collagen deposition and neovascularization, and finally promoted wound healing in diabetic mice. The tTi-EVs also reduced the level of oxidative stress in vitro and in vivo. Besides, the biosafety of tTi-EVs were preliminarily confirmed by blood tests and morphological analysis of major organs. Collectively, the present study proves that tTi-EVs can suppress oxidative stress and facilitate diabetic wound healing, which puts forward a novel function of tTi-EVs and provides potential treatment for diabetic wounds.

Keywords: Diabetes; Oxidative stress; Tumor tissue-derived extracellular vesicles; Wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Diabetes Mellitus, Experimental* / pathology
  • Extracellular Vesicles* / pathology
  • Hydrogen Peroxide
  • Mice
  • Wound Healing / physiology

Substances

  • Hydrogen Peroxide