The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons
Open accessAbstract
Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC-exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC-exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth.
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Cited by
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Self-citationExosomes — beyond stem cells for restorative therapy in stroke and neurological injury
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Metadata
- Authors
- Zhang, Y., Chopp, M., Liu, X. S., Katakowski, M., Wang, X., Tian, X., Wu, D., & Zhang, Z. G.
- Venue
- Molecular Neurobiology
- Published
- 2016-03-19
- Volume
- 54
- Issue
- 4
- Pages
- 2659-2673
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2297436559
- Cited by
- 300
- References
- 79
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, Y., Chopp, M., Liu, X. S., Katakowski, M., Wang, X., Tian, X., Wu, D., & Zhang, Z. G. (2017). Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons. Molecular Neurobiology. https://doi.org/10.1007/s12035-016-9851-0
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