Biomaterial Database

Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. 2019

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

Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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.