Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

Uta Erdbrügger; Charles J. Blijdorp; Irene V. Bijnsdorp; Francesc E. Borràs; Dylan Burger; Benedetta Bussolati; James Brian Byrd; Aled Clayton; James W. Dear; Juan M. Falcón-Pérez; Cristina Grange; Andrew F. Hill; Harry Holthöfer; Ewout J. Hoorn; Guido Jenster; Connie R. Jimenez; Kerstin Junker; John Klein; Mark A. Knepper; Erik H. Koritzinsky; James M. Luther; Metka Lenassi; Janne Leivo; Inge Mertens; Luca Musante; Eline Oeyen; Maija Puhka; Martin E. van Royen; Catherine Sánchez; Carolina Soekmadji; Visith Thongboonkerd; Volkert van Steijn; Gerald Verhaegh; Jason P. Webber; Kenneth Witwer; Peter S.T. Yuen; Lei Zheng; Alicia Llorente; Elena S. Martens-Uzunova

doi:10.1002/jev2.12093

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

Uta Erdbrügger, Charles J. Blijdorp, Irene V. Bijnsdorp, Francesc E. Borràs, Dylan Burger, Benedetta Bussolati, James Brian Byrd, Aled Clayton, James W. Dear, Juan M. Falcón-Pérez, Cristina Grange, Andrew F. Hill, Harry Holthöfer, Ewout J. Hoorn, Guido Jenster, Connie R. Jimenez, Kerstin Junker, John Klein, Mark A. Knepper, Erik H. KoritzinskyJames M. Luther, Metka Lenassi, Janne Leivo, Inge Mertens, Luca Musante, Eline Oeyen, Maija Puhka, Martin E. van Royen, Catherine Sánchez, Carolina Soekmadji, Visith Thongboonkerd, Volkert van Steijn, Gerald Verhaegh, Jason P. Webber, Kenneth Witwer, Peter S.T. Yuen, Lei Zheng, Alicia Llorente, Elena S. Martens-Uzunova^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.

Original language	English
Article number	e12093
Journal	Journal of Extracellular Vesicles
Volume	10
Issue number	7
DOIs	https://doi.org/10.1002/jev2.12093
Publication status	Published - May 2021

Bibliographical note

Funding Information:
ESM‐U, CG, GV, GJ, IVB, MvR, and VvS, are members of the “IMMPROVE” consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015‐8022).

Funding Information:
We thank Karina Barreiro for the transmission electron microscopy images courtesy of Beat DKD project under IMI2, Dr. Kelly Dryden, PhD at the UVA core facility for the cryo-EM images and Dr Benedetta Bussolati, MD for the Super resolution dSTORM images of EVs. Other figures in this manuscript have been created with BioRender.com ESM-U, CG, GV, GJ, IVB, MvR, and VvS, are members of the ?IMMPROVE? consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015-8022). AL is supported by Norges Forskningsr?d, Kreftforeningen and Helse S?r-?st RHF (NO). UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23-HL-126101. CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05.

Funding Information:
UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23‐HL‐126101.

Funding Information:
AL is supported by Norges Forskningsråd, Kreftforeningen and Helse Sør‐Øst RHF (NO).

Funding Information:
CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05.

Publisher Copyright:
© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles

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Urinary extracellular vesicles, A position paper by the Urine Task Force of the International Society for Extracellular VesiclesFinal published version, 2.67 MBLicence: CC BY

Cite this

Erdbrügger, U., Blijdorp, C. J., Bijnsdorp, I. V., Borràs, F. E., Burger, D., Bussolati, B., Byrd, J. B., Clayton, A., Dear, J. W., Falcón-Pérez, J. M., Grange, C., Hill, A. F., Holthöfer, H., Hoorn, E. J., Jenster, G., Jimenez, C. R., Junker, K., Klein, J., Knepper, M. A., ... Martens-Uzunova, E. S. (2021). Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles. Journal of Extracellular Vesicles, 10(7), Article e12093. https://doi.org/10.1002/jev2.12093

@article{afc1e8c07cba4997befa94fa072ade94,

title = "Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles",

abstract = "Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.",

author = "Uta Erdbr{\"u}gger and Blijdorp, {Charles J.} and Bijnsdorp, {Irene V.} and Borr{\`a}s, {Francesc E.} and Dylan Burger and Benedetta Bussolati and Byrd, {James Brian} and Aled Clayton and Dear, {James W.} and Falc{\'o}n-P{\'e}rez, {Juan M.} and Cristina Grange and Hill, {Andrew F.} and Harry Holth{\"o}fer and Hoorn, {Ewout J.} and Guido Jenster and Jimenez, {Connie R.} and Kerstin Junker and John Klein and Knepper, {Mark A.} and Koritzinsky, {Erik H.} and Luther, {James M.} and Metka Lenassi and Janne Leivo and Inge Mertens and Luca Musante and Eline Oeyen and Maija Puhka and {van Royen}, {Martin E.} and Catherine S{\'a}nchez and Carolina Soekmadji and Visith Thongboonkerd and {van Steijn}, Volkert and Gerald Verhaegh and Webber, {Jason P.} and Kenneth Witwer and Yuen, {Peter S.T.} and Lei Zheng and Alicia Llorente and Martens-Uzunova, {Elena S.}",

note = "Funding Information: ESM‐U, CG, GV, GJ, IVB, MvR, and VvS, are members of the “IMMPROVE” consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015‐8022). Funding Information: We thank Karina Barreiro for the transmission electron microscopy images courtesy of Beat DKD project under IMI2, Dr. Kelly Dryden, PhD at the UVA core facility for the cryo-EM images and Dr Benedetta Bussolati, MD for the Super resolution dSTORM images of EVs. Other figures in this manuscript have been created with BioRender.com ESM-U, CG, GV, GJ, IVB, MvR, and VvS, are members of the ?IMMPROVE? consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015-8022). AL is supported by Norges Forskningsr?d, Kreftforeningen and Helse S?r-?st RHF (NO). UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23-HL-126101. CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05. Funding Information: UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23‐HL‐126101. Funding Information: AL is supported by Norges Forskningsr{\aa}d, Kreftforeningen and Helse S{\o}r‐{\O}st RHF (NO). Funding Information: CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05. Publisher Copyright: {\textcopyright} 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles",

year = "2021",

month = may,

doi = "10.1002/jev2.12093",

language = "English",

volume = "10",

journal = "Journal of Extracellular Vesicles",

issn = "2001-3078",

publisher = "Taylor & Francis Ltd",

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Erdbrügger, U, Blijdorp, CJ, Bijnsdorp, IV, Borràs, FE, Burger, D, Bussolati, B, Byrd, JB, Clayton, A, Dear, JW, Falcón-Pérez, JM, Grange, C, Hill, AF, Holthöfer, H, Hoorn, EJ , Jenster, G, Jimenez, CR, Junker, K, Klein, J, Knepper, MA, Koritzinsky, EH, Luther, JM, Lenassi, M, Leivo, J, Mertens, I, Musante, L, Oeyen, E, Puhka, M, van Royen, ME, Sánchez, C, Soekmadji, C, Thongboonkerd, V, van Steijn, V, Verhaegh, G, Webber, JP, Witwer, K, Yuen, PST, Zheng, L, Llorente, A & Martens-Uzunova, ES 2021, 'Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles', Journal of Extracellular Vesicles, vol. 10, no. 7, e12093. https://doi.org/10.1002/jev2.12093

TY - JOUR

T1 - Urinary extracellular vesicles

T2 - A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

AU - Erdbrügger, Uta

AU - Blijdorp, Charles J.

AU - Bijnsdorp, Irene V.

AU - Borràs, Francesc E.

AU - Burger, Dylan

AU - Bussolati, Benedetta

AU - Byrd, James Brian

AU - Clayton, Aled

AU - Dear, James W.

AU - Falcón-Pérez, Juan M.

AU - Grange, Cristina

AU - Hill, Andrew F.

AU - Holthöfer, Harry

AU - Hoorn, Ewout J.

AU - Jenster, Guido

AU - Jimenez, Connie R.

AU - Junker, Kerstin

AU - Klein, John

AU - Knepper, Mark A.

AU - Koritzinsky, Erik H.

AU - Luther, James M.

AU - Lenassi, Metka

AU - Leivo, Janne

AU - Mertens, Inge

AU - Musante, Luca

AU - Oeyen, Eline

AU - Puhka, Maija

AU - van Royen, Martin E.

AU - Sánchez, Catherine

AU - Soekmadji, Carolina

AU - Thongboonkerd, Visith

AU - van Steijn, Volkert

AU - Verhaegh, Gerald

AU - Webber, Jason P.

AU - Witwer, Kenneth

AU - Yuen, Peter S.T.

AU - Zheng, Lei

AU - Llorente, Alicia

AU - Martens-Uzunova, Elena S.

N1 - Funding Information: ESM‐U, CG, GV, GJ, IVB, MvR, and VvS, are members of the “IMMPROVE” consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015‐8022). Funding Information: We thank Karina Barreiro for the transmission electron microscopy images courtesy of Beat DKD project under IMI2, Dr. Kelly Dryden, PhD at the UVA core facility for the cryo-EM images and Dr Benedetta Bussolati, MD for the Super resolution dSTORM images of EVs. Other figures in this manuscript have been created with BioRender.com ESM-U, CG, GV, GJ, IVB, MvR, and VvS, are members of the ?IMMPROVE? consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015-8022). AL is supported by Norges Forskningsr?d, Kreftforeningen and Helse S?r-?st RHF (NO). UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23-HL-126101. CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05. Funding Information: UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23‐HL‐126101. Funding Information: AL is supported by Norges Forskningsråd, Kreftforeningen and Helse Sør‐Øst RHF (NO). Funding Information: CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05. Publisher Copyright: © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles

PY - 2021/5

Y1 - 2021/5

N2 - Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.

AB - Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.

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U2 - 10.1002/jev2.12093

DO - 10.1002/jev2.12093

M3 - Article

C2 - 34035881

AN - SCOPUS:85106448800

SN - 2001-3078

VL - 10

JO - Journal of Extracellular Vesicles

JF - Journal of Extracellular Vesicles

IS - 7

M1 - e12093

ER -

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

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