Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 11, Issue 4, Pages 879-883Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.01.003
Keywords
Biophysical properties; extracellular vesicles; size-exclusion liquid chromatography; ultracentrifugation; ultrafiltration
Funding
- Swedish Research Council (VR-Med)
- Swedish Cancer society
- Swedish Society of Medical Research (SSMF)
- Karolinska Institutet MD/PhD grants
- Agency for Science, Technology and Research (A*STAR), Singapore
- Postdoctoral MOBILITAS Fellowship of the Estonian Science Foundation
- EU IMI (Innovative Medicines Initiative) project COMPACT
- Regenerative Medicine Initiative of the Britain-Israel Research and Academic Exchange Partnership (BIRAX)
- Parkinson's UK [G-1109] Funding Source: researchfish
- The British Council [09BX12PFYR] Funding Source: researchfish
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Extracellular vesicles (EVs) are natural nanoparticles that mediate intercellular transfer of RNA and proteins and are of great medical interest; serving as novel biomarkers and potential therapeutic agents. However, there is little consensus on the most appropriate method to isolate high-yield and high-purity EVs from various biological fluids. Here, we describe a systematic comparison between two protocols for EV purification: ultrafiltration with subsequent liquid chromatography (UF-LC) and differential ultracentrifugation (UC). A significantly higher EV yield resulted from UF-LC as compared to UC, without affecting vesicle protein composition. Importantly, we provide novel evidence that, in contrast to UC-purified EVs, the biophysical properties of UF-LC-purified EVs are preserved, leading toadifferent in vivo biodistribution, with less accumulation in lungs. Finally, we show that UF-LC is scalable and adaptable for EV isolation from complex media types such as stem cell media, which is of huge significance for future clinical applications involving EVs. (C) 2015 The Authors. Published by Elsevier Inc.
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