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

Alter, Claudio Luca; Detampel, Pascal; Schefer, Roman Basil; Claudia, Lotter,; Hauswirth, Patrick; Puligilla, Ramya Deepthi; Weibel, Vera Jo; Schenk, Susanne; Heusermann, Wolf; Schürz, Melanie; Meisner‐Kober, Nicole; Palivan, Cornelia G.; Einfalt, Tomaz; Huwyler, Jörg

doi:10.1038/s42003-023-04859-2

Cited by 4 publications

(4 citation statements)

References 123 publications

(153 reference statements)

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“…43 This protocol resulted in blebs with cell-like mechanical properties 44 that were then extruded to produce 200nm-diameter ‘large’ plasma membrane vesicles (LPMVs). 45…”

Section: Resultsmentioning

confidence: 99%

“…43 This protocol resulted in blebs with cell-like mechanical properties 44 that were then extruded to produce 200nm-diameter 'large' plasma membrane vesicles (LPMVs). 45 Figure 1, Schematic diagram of experimental approach to produce EVs and LPMVs. EVs are collected from the supernatant of cultured MDA-MB-231 cells and are purified with SEC (upper path).…”

Section: Evs and Plasma Membrane Vesicles: Collection Synthesis And C...mentioning

confidence: 99%

“…While it is possible that this difference in mobility is due to the difference in membrane composition between EVs and LPMVs, it must be noted that the vesiculation agent, NEM can irreversibly react with and modify cysteines and thiol groups, 43 leading to changes in the membrane constituents of LPMVs. Despite this drawback, the use of NEM to produce plasma membrane vesicles seems a better option for maintaining protein integrity compared to other protocols that use paraformaldehyde and dithiothreitol as vesiculation agents, 45,71 which would result in protein crosslinking and fixation.…”

Section: Ev Mobility In Collagen Hydrogelsmentioning

confidence: 99%

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Extracellular vesicle mobility in collagen I hydrogels is modulated by RGD-binding integrins

Tam,

Becker,

Mangiarotti

et al. 2024

Preprint

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Extracellular vesicles (EVs) are a diverse population of membrane structures produced and released by cells into the extracellular space for the intercellular trafficking of cargo molecules. They are implicated in various biological processes, including angiogenesis, immunomodulation, and cancer cell signaling. While much research has focused on their biogenesis or their effects on recipient cells, less is understood about how EVs are capable of traversing diverse tissue environments and crossing biological barriers. Their interactions with extracellular matrix components are of particular interest, as such interactions govern diffusivity and mobility, providing a potential basis for organotropism. To start to untangle how EV-matrix interactions affect diffusivity, we use highspeed epifluorescence microscopy, single particle tracking, and confocal reflectance microscopy to analyze particle mobility and localization in extracellular matrix-mimicking hydrogels composed of collagen I. EVs are compared with synthetic liposomes and extruded plasma membrane vesicles to better understand the importance of membrane composition on these interactions. By treating EVs with trypsin to digest surface proteins, we determine that proteins are primarily responsible for EV immobilization in collagen I hydrogels. We next use a synthetic peptide competitive inhibitor to narrow down the identity of the proteins involved to argynylglycylaspartic acid (RGD) motif-binding integrins, which interact with unincorporated or denatured non-fibrillar collagen. Moreover, the effect of integrin inhibition with RGD peptides has strong implications for the use of RGD-peptide-based drugs to treat certain cancers, as integrin inhibition appears to increase EV mobility, improving their ability to infiltrate tissue-like environments.

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“…43 This protocol resulted in blebs with cell-like mechanical properties 44 that were then extruded to produce 200nm-diameter ‘large’ plasma membrane vesicles (LPMVs). 45…”

Section: Resultsmentioning

confidence: 99%

Section: Evs and Plasma Membrane Vesicles: Collection Synthesis And C...mentioning

confidence: 99%

Section: Ev Mobility In Collagen Hydrogelsmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular vesicle mobility in collagen I hydrogels is modulated by RGD-binding integrins

Tam,

Becker,

Mangiarotti

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…EVs were once thought to function as cellular garbage disposals [ 2 ], but it is now accepted that EVs play an important role in cellular communication [ 3 , 4 , 5 ], intracellular signaling [ 6 , 7 , 8 ], and cellular differentiation [ 9 , 10 , 11 ]. In addition, EVs are used in multiple applications [ 12 , 13 , 14 ]. EVs isolated from biological fluids including urine [ 15 ], plasma [ 16 ], and cerebrospinal fluid [ 17 ] represent a rich source of biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles: Investigating the Pathophysiology of Diabetes-Associated Hypertension and Diabetic Nephropathy

Alli

2023

Biology

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Extracellular vesicles (EVs) include exosomes, microvesicles, and apoptotic bodies. EVs are released by all cell types and are found in biological fluids including plasma and urine. Urinary extracellular vesicles (uEVs) are a mixed population of EVs that comprise small EVs that are filtered and excreted, EVs secreted by tubular epithelial cells, and EVs released from the bladder, urethra, and prostate. The packaged cargo within uEVs includes bioactive molecules such as metabolites, lipids, proteins, mRNAs, and miRNAs. These molecules are involved in intercellular communication, elicit changes in intracellular signaling pathways, and play a role in the pathogenesis of various diseases including diabetes-associated hypertension and diabetic nephropathy. uEVs represent a rich source of biomarkers, prognosis markers, and can be loaded with small-molecule drugs as a vehicle for delivery.

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Harnessing Engineered Extracellular Vesicles from Mesenchymal Stem Cells as Therapeutic Scaffolds for Bone‐Related Diseases

Yu,

Wang,

Zhou

et al. 2024

Adv Funct Materials

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Mesenchymal stem cells (MSCs) play a crucial role in maintaining bone homeostasis and are extensively explored for cell therapy in various bone‐related diseases. In addition to direct cell therapy, the secretion of extracellular vesicles (EVs) by MSCs has emerged as a promising alternative approach. MSC‐derived EVs (MSC‐EVs) offer equivalent therapeutic efficacy to MSCs while mitigating potential risks. These EVs possess unique properties that enable them to traverse biological barriers and deliver bioactive cargos to target cells. Furthermore, by employing modification and engineering strategies, the therapeutic effects and tissue targeting specificity of MSC‐EVs can be further enhanced to meet specific therapeutic needs. In this review, the mechanisms and advantages of MSC‐EV therapy in diseased bone tissues are highlighted. Through simple isolation and modification techniques, MSC‐EV‐based biomaterials have demonstrated great promise for bone regeneration. Finally, future perspectives on MSC‐EV therapy are presented, envisioning the development of next‐generation regenerative materials and bioactive agents for clinical translation in the field of bone regeneration.

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

Cited by 4 publications

References 123 publications

Extracellular vesicle mobility in collagen I hydrogels is modulated by RGD-binding integrins

Extracellular vesicle mobility in collagen I hydrogels is modulated by RGD-binding integrins

Extracellular Vesicles: Investigating the Pathophysiology of Diabetes-Associated Hypertension and Diabetic Nephropathy

Harnessing Engineered Extracellular Vesicles from Mesenchymal Stem Cells as Therapeutic Scaffolds for Bone‐Related Diseases

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