Imperial College London
Alternate

Professor Molly Stevens

Faculty of Engineering, Department of Materials

Professor of Biomedical Materials and Regenerative Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6804m.stevens

 
 
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Location

 

208Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Whittaker:2020:10.1080/20013078.2020.1807674,
author = {Whittaker, T and Nagelkerke, A and Nele, V and Kauscher, U and Stevens, M},
doi = {10.1080/20013078.2020.1807674},
journal = {Journal of Extracellular Vesicles},
title = {Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles},
url = {http://dx.doi.org/10.1080/20013078.2020.1807674},
volume = {9},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - It has been demonstrated that some commonly used Extracellular Vesicle (EV) isolation techniques can lead to substantial contamination with non-EV factors. Whilst it has been established that this impacts the identification of biomarkers, the impact on apparent EV bioactivity has not been explored. Extracellular vesicles have been implicated as critical mediators of therapeutic human mesenchymal stem cell (hMSC) paracrine signalling. Isolated hMSC-EVs have been used to treat multiple in vitro and in vivo models of tissue damage. However, the relative contributions of EVs and non-EV factors have not been directly compared. The dependence of hMSC paracrine signalling on EVs was first established by ultrafiltration of hMSC-conditioned medium to deplete EVs, which led to a loss of signalling activity. Here, we show that this method also causes depletion of non-EV factors, and that when this is prevented proangiogenic signalling activity is fully restored in vitro. Subsequently, we used size-exclusion chromatography (SEC) to separate EVs and soluble proteins to directly and quantitatively compare their relative contributions to signalling. Non-EV factors were found to be necessary and sufficient for the stimulation of angiogenesis and wound healing in vitro. EVs in isolation were found to be capable of potentiating signalling only when isolated by a low-purity method, or when used at comparatively high concentrations. These results indicate a potential for contaminating soluble factors to artefactually increase the apparent bioactivity of EV isolates and could have implications for future studies on the biological roles of EVs.
AU  - Whittaker,T
AU  - Nagelkerke,A
AU  - Nele,V
AU  - Kauscher,U
AU  - Stevens,M
DO  - 10.1080/20013078.2020.1807674
PY  - 2020///
SN  - 2001-3078
TI  - Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles
T2  - Journal of Extracellular Vesicles
UR  - http://dx.doi.org/10.1080/20013078.2020.1807674
UR  - http://hdl.handle.net/10044/1/81914
VL  - 9
ER  -
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