Journal of Extracellular Vesicles (Dec 2019)

Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications

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

DOI
https://doi.org/10.1080/20013078.2019.1609206
Journal volume & issue
Vol. 8, no. 1

Abstract

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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.

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