Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes

Int J Mol Sci. 2021 Apr 8;22(8):3851. doi: 10.3390/ijms22083851.

Abstract

Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.

Keywords: MSC; adipose; bone marrow; cargo; diabetes; exosome; extracellular vesicle; mesenchymal; therapy; wound healing.

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Bone Marrow Cells
  • Diabetes Complications / therapy*
  • Exosomes / metabolism
  • Exosomes / ultrastructure
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / ultrastructure
  • Flow Cytometry
  • Gene Expression Profiling
  • Immunohistochemistry
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Ulcer / etiology*
  • Ulcer / therapy*
  • Wound Healing*