Witwer Kenneth W, Van Balkom Bas W M, 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
Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Extracell Vesicles. 2019 Apr 29;8(1):1609206. doi: 10.1080/20013078.2019.1609206. eCollection 2019.
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 and 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.
间充质基质/干细胞（MSC）来源的小细胞外囊泡（sEV）正迅速走向临床应用。然而，由于多种因素，关于MSC-sEV的生物学特性、功能和效力出现了差异和争议：MSC的多样性及其制备方法；sEV产生和分离的各种方法；缺乏标准化的质量保证检测方法；以及功能检测的可重复性有限。为了解决这些问题，四个学会（SOCRATES、ISEV、ISCT和ISBT）的成员提出了针对MSC-sEV的具体协调标准，以促进数据共享和比较，这应有助于推动该领域向临床应用发展。具体而言，MSC-sEV应通过可量化指标来定义，以确定制剂中sEV的细胞来源、脂质膜囊泡的存在以及囊泡的物理和生化完整性程度。出于实际目的，新的MSC-sEV制剂也可与特征明确的MSC-sEV生物学参考物进行比较。制定这些指标的最终目标是将MSC-sEV生物学和治疗效力的各个方面映射到每种制剂的可量化特征上。
