Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization

Aisha Khan,1,2 Julia Oliveira,2 Yee-Shuan Lee,1 James D Guest,2,3 Risset Silvera,2 Yelena Pressman,2 Damien D Pearse,2,3 Adriana E Nettina,1,2 Pascal J Goldschmidt-Clermont,4 Hassan Al-Ali,2 Indigo Williams,2 Allan D Levi,2,3 W Dalton Dietrich2,3 1Interdisciplinary Stem Cell Institute, Miller School...

Full description

Saved in:
Bibliographic Details
Main Authors: Khan A, Oliveira J, Lee YS, Guest JD, Silvera R, Pressman Y, Pearse DD, Nettina AE, Goldschmidt-Clermont PJ, Al-Ali H, Williams I, Levi AD, Dietrich WD
Format: Article
Language:English
Published: Dove Medical Press 2025-04-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/human-schwann-cell-derived-extracellular-vesicle-isolation-bioactivity-peer-reviewed-fulltext-article-IJN
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849701653709586432
author Khan A
Oliveira J
Lee YS
Guest JD
Silvera R
Pressman Y
Pearse DD
Nettina AE
Goldschmidt-Clermont PJ
Al-Ali H
Williams I
Levi AD
Dietrich WD
author_facet Khan A
Oliveira J
Lee YS
Guest JD
Silvera R
Pressman Y
Pearse DD
Nettina AE
Goldschmidt-Clermont PJ
Al-Ali H
Williams I
Levi AD
Dietrich WD
author_sort Khan A
collection DOAJ
description Aisha Khan,1,2 Julia Oliveira,2 Yee-Shuan Lee,1 James D Guest,2,3 Risset Silvera,2 Yelena Pressman,2 Damien D Pearse,2,3 Adriana E Nettina,1,2 Pascal J Goldschmidt-Clermont,4 Hassan Al-Ali,2 Indigo Williams,2 Allan D Levi,2,3 W Dalton Dietrich2,3 1Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USA; 2The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL, USA; 3Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA; 4Miller School of Medicine, University of Miami, Miami, FL, USACorrespondence: Aisha Khan, Email akhan@med.miami.eduPurpose: Schwann cell-derived extracellular vesicles (SCEVs) have demonstrated favorable effects in spinal cord, peripheral nerve, and brain injuries. Herein, a scalable, standardized, and efficient isolation methodology of SCEVs obtaining a high yield with a consistent composition as measured by proteomic, lipidomic, and miRNA analysis of their content is described for future clinical use.Methods: Human Schwann cells were obtained ethically from nine donors and cultured in a defined growth medium optimized for proliferation. At confluency, the culture was replenished with an isolation medium for 48 hours, then collected and centrifuged sequentially at low and ultra-high speeds to collect purified EVs. The EVs were characterized with mass spectrometry to identify and quantify proteins, lipidomic analysis to assess lipid composition, and next-generation sequencing to confirm miRNA profiles. Each batch of EVs was assessed to ensure their therapeutic potential in promoting neurite outgrowth and cell survival.Results: High yields of SCEVs were consistently obtained with similar comprehensive molecular profiles across samples, indicating the reproducibility and reliability of the isolation method. Bioactivity to increase neurite process growth was confirmed in vitro. The predominance of triacylglycerol and phosphatidylcholine suggested its role in cellular membrane dynamics essential for axon regeneration and inflammation mitigation. Of the 2517 identified proteins, 136 were closely related to nervous system repair and regeneration. A total of 732 miRNAs were cataloged, with the top 30 miRNAs potentially contributing to axon growth, neuroprotection, myelination, angiogenesis, the attenuation of neuroinflammation, and key signaling pathways such as VEGFA-VEGFR2 and PI3K-Akt signaling, which are crucial for nervous system repair.Conclusion: The study establishes a robust framework for SCEV isolation and their comprehensive characterization, which is consistent with their therapeutic potential in neurological applications. This work provides a valuable proteomic, lipidomic, and miRNA dataset to inform future advancements in applying SCEV to the experimental treatment of neurological injuries and diseases.Keywords: myelination, axon growth, neuroprotection, regeneration, lipidomic
format Article
id doaj-art-873c39d75eaa4d449d197e67b7414966
institution DOAJ
issn 1178-2013
language English
publishDate 2025-04-01
publisher Dove Medical Press
record_format Article
series International Journal of Nanomedicine
spelling doaj-art-873c39d75eaa4d449d197e67b74149662025-08-20T03:17:52ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-04-01Volume 2041234144101774Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics CharacterizationKhan AOliveira JLee YSGuest JDSilvera RPressman YPearse DDNettina AEGoldschmidt-Clermont PJAl-Ali HWilliams ILevi ADDietrich WDAisha Khan,1,2 Julia Oliveira,2 Yee-Shuan Lee,1 James D Guest,2,3 Risset Silvera,2 Yelena Pressman,2 Damien D Pearse,2,3 Adriana E Nettina,1,2 Pascal J Goldschmidt-Clermont,4 Hassan Al-Ali,2 Indigo Williams,2 Allan D Levi,2,3 W Dalton Dietrich2,3 1Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USA; 2The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL, USA; 3Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA; 4Miller School of Medicine, University of Miami, Miami, FL, USACorrespondence: Aisha Khan, Email akhan@med.miami.eduPurpose: Schwann cell-derived extracellular vesicles (SCEVs) have demonstrated favorable effects in spinal cord, peripheral nerve, and brain injuries. Herein, a scalable, standardized, and efficient isolation methodology of SCEVs obtaining a high yield with a consistent composition as measured by proteomic, lipidomic, and miRNA analysis of their content is described for future clinical use.Methods: Human Schwann cells were obtained ethically from nine donors and cultured in a defined growth medium optimized for proliferation. At confluency, the culture was replenished with an isolation medium for 48 hours, then collected and centrifuged sequentially at low and ultra-high speeds to collect purified EVs. The EVs were characterized with mass spectrometry to identify and quantify proteins, lipidomic analysis to assess lipid composition, and next-generation sequencing to confirm miRNA profiles. Each batch of EVs was assessed to ensure their therapeutic potential in promoting neurite outgrowth and cell survival.Results: High yields of SCEVs were consistently obtained with similar comprehensive molecular profiles across samples, indicating the reproducibility and reliability of the isolation method. Bioactivity to increase neurite process growth was confirmed in vitro. The predominance of triacylglycerol and phosphatidylcholine suggested its role in cellular membrane dynamics essential for axon regeneration and inflammation mitigation. Of the 2517 identified proteins, 136 were closely related to nervous system repair and regeneration. A total of 732 miRNAs were cataloged, with the top 30 miRNAs potentially contributing to axon growth, neuroprotection, myelination, angiogenesis, the attenuation of neuroinflammation, and key signaling pathways such as VEGFA-VEGFR2 and PI3K-Akt signaling, which are crucial for nervous system repair.Conclusion: The study establishes a robust framework for SCEV isolation and their comprehensive characterization, which is consistent with their therapeutic potential in neurological applications. This work provides a valuable proteomic, lipidomic, and miRNA dataset to inform future advancements in applying SCEV to the experimental treatment of neurological injuries and diseases.Keywords: myelination, axon growth, neuroprotection, regeneration, lipidomichttps://www.dovepress.com/human-schwann-cell-derived-extracellular-vesicle-isolation-bioactivity-peer-reviewed-fulltext-article-IJNmyelinationaxon growthneuroprotectionregenerationlipidomic.
spellingShingle Khan A
Oliveira J
Lee YS
Guest JD
Silvera R
Pressman Y
Pearse DD
Nettina AE
Goldschmidt-Clermont PJ
Al-Ali H
Williams I
Levi AD
Dietrich WD
Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization
International Journal of Nanomedicine
myelination
axon growth
neuroprotection
regeneration
lipidomic.
title Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization
title_full Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization
title_fullStr Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization
title_full_unstemmed Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization
title_short Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization
title_sort human schwann cell derived extracellular vesicle isolation bioactivity assessment and omics characterization
topic myelination
axon growth
neuroprotection
regeneration
lipidomic.
url https://www.dovepress.com/human-schwann-cell-derived-extracellular-vesicle-isolation-bioactivity-peer-reviewed-fulltext-article-IJN
work_keys_str_mv AT khana humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT oliveiraj humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT leeys humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT guestjd humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT silverar humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT pressmany humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT pearsedd humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT nettinaae humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT goldschmidtclermontpj humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT alalih humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT williamsi humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT leviad humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization
AT dietrichwd humanschwanncellderivedextracellularvesicleisolationbioactivityassessmentandomicscharacterization