Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons

Int J Mol Sci. 2021 Nov 16;22(22):12373. doi: 10.3390/ijms222212373.

Abstract

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

Keywords: adipose-derived stem cells; extracellular vesicles; tendon healing; tendon regeneration.

MeSH terms

  • Achilles Tendon / injuries*
  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Animals
  • Biglycan / genetics
  • Biglycan / metabolism
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Decorin / genetics
  • Decorin / metabolism
  • Extracellular Vesicles / chemistry
  • Extracellular Vesicles / transplantation*
  • Female
  • Gene Expression
  • Rabbits
  • Stem Cells / chemistry*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Tendon Injuries / metabolism
  • Tendon Injuries / pathology
  • Tendon Injuries / therapy*
  • Tenocytes / cytology
  • Tenocytes / metabolism
  • Treatment Outcome
  • Wound Healing / physiology*

Substances

  • Biglycan
  • Biomarkers
  • Decorin