Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications Academic Article uri icon


  • Small extracellular vesicles (sEVs) from mesenchymal stromal/stem cells (MSCs) are transiting rapidly towards clinical applications. However, discrepancies and controversies about the biology, functions, and potency of MSC-sEVs have arisen due to several factors: the diversity of MSCs and their preparation; various methods of sEV production and separation; a lack of standardized quality assurance assays; and limited reproducibility of in vitro and in vivo functional assays. To address these issues, members of four societies (SOCRATES, ISEV, ISCT and ISBT) propose specific harmonization criteria for MSC-sEVs to facilitate data sharing and comparison, which should help to advance the field towards clinical applications. Specifically, MSC-sEVs should be defined by quantifiable metrics to identify the cellular origin of the sEVs in a preparation, presence of lipid-membrane vesicles, and the degree of physical and biochemical integrity of the vesicles. For practical purposes, new MSC-sEV preparations might also be measured against a well-characterized MSC-sEV biological reference. The ultimate goal of developing these metrics is to map aspects of MSC-sEV biology and therapeutic potency onto quantifiable features of each preparation.


  • Witwer, Kenneth W
  • Van Balkom, Bas WM
  • Bruno, Stefania
  • Choo, Andre
  • Dominici, Massimo
  • Gimona, Mario
  • Hill, Andrew F
  • De Kleijn, Dominique
  • Koh, Mickey
  • Lai, Ruenn Chai
  • Mitsialis, S Alex
  • Ortiz, Luis A
  • Rohde, Eva
  • Asada, Takashi
  • Toh, Wei Seong
  • Weiss, Daniel J
  • Zheng, Lei
  • Giebel, Bernd
  • Lim, Sai Kiang

publication date

  • 2019