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  Extracellular vesicles derived from neural progenitor cells: A preclinical evaluation for stroke treatment in mice

Zheng, X., Zhang, L., Kuang, Y., Venkataramani, V., Jin, F., Hein, K., et al. (2020). Extracellular vesicles derived from neural progenitor cells: A preclinical evaluation for stroke treatment in mice. Translational Stroke Research, In Press. doi:10.1007/s12975-020-00814-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-66B3-C Version Permalink: http://hdl.handle.net/21.11116/0000-0007-66B8-7
Genre: Journal Article

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 Creators:
Zheng, X., Author
Zhang, L., Author
Kuang, Y., Author
Venkataramani, V., Author
Jin, F., Author
Hein, K., Author
Zafeiriou, M. P., Author
Lenz, C.1, Author              
Moebius, W., Author
Kilic, E., Author
Hermann, D. M., Author
Weber, M. S., Author
Urlaub, H.2, Author              
Zimmermann, W.-H., Author
Bähr, M., Author
Doeppner, T. R., Author
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: Cerebral ischemia; Extracellular vesicles; Neural progenitor cells; Neurological recovery; Neuroregeneration
 Abstract: Stem cells such as mesenchymal stem cells (MSCs) enhance neurological recovery in preclinical stroke models by secreting extracellular vesicles (EVs). Since previous reports have focused on the application of MSC-EVs only, the role of the most suitable host cell for EV enrichment and preclinical stroke treatment remains elusive. The present study aimed to evaluate the therapeutic potential of EVs derived from neural progenitor cells (NPCs) following experimental stroke. Using the PEG technique, EVs were enriched and characterized by electron microscopy, proteomics, rt-PCR, nanosight tracking analysis, and Western blotting. Different dosages of NPC-EVs displaying a characteristic profile in size, shape, cargo protein, and non-coding RNA contents were incubated in the presence of cerebral organoids exposed to oxygen-glucose deprivation (OGD), significantly reducing cell injury when compared with control organoids. Systemic administration of NPC-EVs in male C57BL6 mice following experimental ischemia enhanced neurological recovery and neuroregeneration for as long as 3 months. Interestingly, the therapeutic impact of such NPC-EVs was found to be not inferior to MSC-EVs. Flow cytometric analyses of blood and brain samples 7 days post-stroke demonstrated increased blood concentrations of B and T lymphocytes after NPC-EV delivery, without affecting cerebral cell counts. Likewise, a biodistribution analysis after systemic delivery of NPC-EVs revealed the majority of NPC-EVs to be found in extracranial organs such as the liver and the lung. This proof-of-concept study supports the idea of EVs being a general concept of stem cell–induced neuroprotection under stroke conditions, where EVs contribute to reverting the peripheral post-stroke immunosuppression.

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Language(s): eng - English
 Dates: 2020-05-02
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1007/s12975-020-00814-z
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Title: Translational Stroke Research
Source Genre: Journal
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Pages: 19 Volume / Issue: - Sequence Number: In Press Start / End Page: - Identifier: -