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

TLDR

Small extracellular vesicles from mesenchymal stromal cells are rapidly moving toward clinical use, yet controversies arise from MSC heterogeneity, varied production and separation methods, and a lack of standardized quality assays that limit reproducibility. The authors propose harmonization criteria from four societies to enable data sharing and comparison, aiming to map MSC‑sEV biology and therapeutic potency onto measurable preparation features. They recommend defining MSC‑sEVs by quantifiable metrics—cellular origin, lipid‑membrane vesicle presence, and physical/biochemical integrity—and suggest benchmarking against a well‑characterized reference preparation.

Abstract

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.