Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles

J Transl Med. 2016 Feb 2:14:34. doi: 10.1186/s12967-016-0794-z.


Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise macrophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of ​lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms.

MeSH terms

  • Cell Polarity* / drug effects
  • Extracellular Vesicles / drug effects
  • Extracellular Vesicles / metabolism*
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Paracrine Communication* / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • Umbilical Cord / cytology


  • Lipopolysaccharides
  • Toll-Like Receptor 4