Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons
Yi Zhang,Michael Chopp,Michael Chopp,Xian Shuang Liu,Mark Katakowski,Xinli Wang,Xinchu Tian,David Wu,Zheng Gang Zhang +8 more
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TLDR
Using primary cortical neurons cultured in a microfluidic device, it is found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in M SCs abolished their effect on axonalgrowth.Abstract:
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.read more
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Concise Review: MSC-Derived Exosomes for Cell-Free Therapy
TL;DR: T careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell‐free MSC‐based therapies with decreased risk.
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Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.
Tian Tian,Huixin Zhang,Chunpeng He,Song Fan,Yanliang Zhu,Cui Qi,Ning-Ping Huang,Zhongdang Xiao,Zuhong Lu,Bakhos A. Tannous,Jun Gao +10 more
TL;DR: The engineered c(RGDyK)-conjugated exosomes (cRGD-Exo) target the lesion region of the ischemic brain after intravenous administration and provide a strategy for the rapid and large-scale production of functionalized exosome.
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Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes
TL;DR: The history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges are discussed.
Journal ArticleDOI
MicroRNA cluster miR-17-92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats.
Hongqi Xin,Mark Katakowski,Fengjie Wang,Jian Yong Qian,Xian Shuang Liu,Meser M. Ali,Benjamin Buller,Zheng Gang Zhang,Michael Chopp +8 more
TL;DR: Treatment of stroke with tailored exosomes enriched with the miR-17–92 cluster increases neural plasticity and functional recovery after stroke, possibly via targeting phosphatase and tensin homolog to activate the PI3K/protein kinase B/mechanistic target of rapamycin/glycogen synthase kinase 3&bgr; signaling pathway.
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Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury
TL;DR: The evidence that exosomes could be used as a neurorestorative therapy after stroke or traumatic brain injury is discussed and how engineering of their microRNA cargo could optimize this approach.
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