دورية أكاديمية
Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons
| العنوان: | Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons |
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| المؤلفون: | Zhang, Yi, Chopp, Michael, Liu, Xian S, Katakowski, Mark, Wang, Xinli, Tian, Xinchu, Wu, David, Zhang, Zhenggang |
| المصدر: | Neurology Articles |
| بيانات النشر: | Henry Ford Health Scholarly Commons |
| سنة النشر: | 2017 |
| المجموعة: | Henry Ford Health System Scholarly Commons |
| مصطلحات موضوعية: | Animals, Argonaute Proteins, Axons, Botulinum Toxins, Chondroitin Sulfate Proteoglycans, Endocytosis, Exosomes, Mesenchymal Stem Cells, MicroRNAs, Rats, Wistar, SNARE Proteins, Signal Transduction |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://scholarlycommons.henryford.com/neurology_articles/312Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:26993303Test |
| الإتاحة: | https://scholarlycommons.henryford.com/neurology_articles/312Test http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:26993303Test |
| رقم الانضمام: | edsbas.AB7A2621 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |