High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications

Abstract Extracellular vesicles (EVs) are highly interesting for the design of next-generation therapeutics. However, their preparation methods face challenges in standardization, yield, and reproducibility. Here, we describe a highly efficient and reproducible EV preparation method for monodisperse...

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Main Authors: Claudio L. Alter, Pascal Detampel, Roman B. Schefer, Claudia Lotter, Patrick Hauswirth, Ramya D. Puligilla, Vera J. Weibel, Susanne H. Schenk, Wolf Heusermann, Melanie Schürz, Nicole Meisner-Kober, Cornelia Palivan, Tomaž Einfalt, Jörg Huwyler
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-023-04859-2
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author Claudio L. Alter
Pascal Detampel
Roman B. Schefer
Claudia Lotter
Patrick Hauswirth
Ramya D. Puligilla
Vera J. Weibel
Susanne H. Schenk
Wolf Heusermann
Melanie Schürz
Nicole Meisner-Kober
Cornelia Palivan
Tomaž Einfalt
Jörg Huwyler
author_facet Claudio L. Alter
Pascal Detampel
Roman B. Schefer
Claudia Lotter
Patrick Hauswirth
Ramya D. Puligilla
Vera J. Weibel
Susanne H. Schenk
Wolf Heusermann
Melanie Schürz
Nicole Meisner-Kober
Cornelia Palivan
Tomaž Einfalt
Jörg Huwyler
author_sort Claudio L. Alter
collection DOAJ
description Abstract Extracellular vesicles (EVs) are highly interesting for the design of next-generation therapeutics. However, their preparation methods face challenges in standardization, yield, and reproducibility. Here, we describe a highly efficient and reproducible EV preparation method for monodisperse nano plasma membrane vesicles (nPMVs), which yields 10 to 100 times more particles per cell and hour than conventional EV preparation methods. nPMVs are produced by homogenizing giant plasma membrane vesicles following cell membrane blebbing and apoptotic body secretion induced by chemical stressors. nPMVs showed no significant differences compared to native EVs from the same cell line in cryo-TEM analysis, in vitro cellular interactions, and in vivo biodistribution studies in zebrafish larvae. Proteomics and lipidomics, on the other hand, suggested substantial differences consistent with the divergent origin of these two EV types and indicated that nPMVs primarily derive from apoptotic extracellular vesicles. nPMVs may provide an attractive source for developing EV-based pharmaceutical therapeutics.
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spelling doaj.art-be10fbb715fc4794919ad22eb4023b742023-05-07T11:20:55ZengNature PortfolioCommunications Biology2399-36422023-05-016111710.1038/s42003-023-04859-2High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applicationsClaudio L. Alter0Pascal Detampel1Roman B. Schefer2Claudia Lotter3Patrick Hauswirth4Ramya D. Puligilla5Vera J. Weibel6Susanne H. Schenk7Wolf Heusermann8Melanie Schürz9Nicole Meisner-Kober10Cornelia Palivan11Tomaž Einfalt12Jörg Huwyler13Department of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselImaging Core Facility, University of BaselDepartment of Biosciences & Medical Biology, University of SalzburgDepartment of Biosciences & Medical Biology, University of SalzburgDepartment of Chemistry, University of BaselDepartment of Pharmaceutical Technology, University of BaselDepartment of Pharmaceutical Technology, University of BaselAbstract Extracellular vesicles (EVs) are highly interesting for the design of next-generation therapeutics. However, their preparation methods face challenges in standardization, yield, and reproducibility. Here, we describe a highly efficient and reproducible EV preparation method for monodisperse nano plasma membrane vesicles (nPMVs), which yields 10 to 100 times more particles per cell and hour than conventional EV preparation methods. nPMVs are produced by homogenizing giant plasma membrane vesicles following cell membrane blebbing and apoptotic body secretion induced by chemical stressors. nPMVs showed no significant differences compared to native EVs from the same cell line in cryo-TEM analysis, in vitro cellular interactions, and in vivo biodistribution studies in zebrafish larvae. Proteomics and lipidomics, on the other hand, suggested substantial differences consistent with the divergent origin of these two EV types and indicated that nPMVs primarily derive from apoptotic extracellular vesicles. nPMVs may provide an attractive source for developing EV-based pharmaceutical therapeutics.https://doi.org/10.1038/s42003-023-04859-2
spellingShingle Claudio L. Alter
Pascal Detampel
Roman B. Schefer
Claudia Lotter
Patrick Hauswirth
Ramya D. Puligilla
Vera J. Weibel
Susanne H. Schenk
Wolf Heusermann
Melanie Schürz
Nicole Meisner-Kober
Cornelia Palivan
Tomaž Einfalt
Jörg Huwyler
High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
Communications Biology
title High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
title_full High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
title_fullStr High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
title_full_unstemmed High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
title_short High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
title_sort high efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications
url https://doi.org/10.1038/s42003-023-04859-2
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