Biological reference materials for extracellular vesicle studies

详细信息    查看全文

• 作者：S. Valkonen^a ; ^b ; ^{sami.valkonen@helsinki.fi} ; E. van der Pol^c ; ^d ; A. Bö ; ing^c ; Y. Yuana^c ; M. Yliperttula^e ; ^f ; R. Nieuwland^c ; S. Laitinen^b ; P.R.M. Siljander^a
• 关键词：Extracellular vesicles ; Nanoerythrosome ; Reference material ; Standardization ; Characterization ; Quantification
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：98
• 期：Complete
• 页码：4-16
• 全文大小：2082 K
• 卷排序：98

文摘

Extracellular vesicles (EVs) mediate normal physiological homeostasis and pathological processes by facilitating intercellular communication. Research of EVs in basic science and clinical settings requires both methodological standardization and development of reference materials (RM). Here, we show insights and results of biological RM development for EV studies. We used a three-step approach to find and develop a biological RM. First, a literature search was done to find candidates for biological RMs. Second, a questionnaire was sent to EV researchers querying the preferences for RM and their use. Third, a biological RM was selected, developed, characterized, and evaluated.The responses to the survey demonstrated a clear and recognized need for RM optimized for the calibration of EV measurements. Based on the literature, naturally occurring and produced biological RM, such as virus particles and liposomes, were proposed as RM. However, none of these candidate RMs have properties completely matching those of EVs, such as size and refractive index distribution. Therefore, we evaluated the use of nanoerythrosomes (NanoE), vesicles produced from erythrocytes, as a potential biological RM. The strength of NanoE is their resemblance to EVs. Compared to the erythrocyte-derived EVs (eryEVs), NanoE have similar morphology, a similar refractive index (1.37), larger diameter (70% of the NanoE are over 200 nm), and increased positive staining for CD235a and lipids (Di-8-ANEPPS) (58% and 67% in NanoE vs. 21% and 45% in eryEVs, respectively).Altogether, our results highlight the general need to develop and validate new RM with similar physical and biochemical properties as EVs to standardize EV measurements between instruments and laboratories.