Exosomes Derived From miR-133b-Modified Mesenchymal Stem Cells Promote Recovery After Spinal Cord Injury

Dong, Li; Zhang, Peng; Yao, Xiyang; Li, Haiying; Shen, Haitao; Li, Xiang; Wu, Jiang; Lu, Xiaocheng

doi:10.3389/fnins.2018.00845

Cited by 138 publications

(130 citation statements)

References 54 publications

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“…Of note, exosomes released by glial cells in the PNS have shown to promote robust axonal regeneration and survival (Lopez‐Leal and Court ). A similar result was obtained from mesenchymal stem cells releasing exosomes following spinal cord injury (Li et al ; Liu et al ).…”

Section: Axonal Regenerationsupporting

confidence: 82%

Construction and reconstruction of brain circuits: normal and pathological axon guidance

Roig‐Puiggros

Vigouroux

Beckman

et al. 2019

Journal of Neurochemistry

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Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the CNS as well as the PNS must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, while these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields.

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Section: Axonal Regenerationsupporting

confidence: 82%

Construction and reconstruction of brain circuits: normal and pathological axon guidance

Roig‐Puiggros

Vigouroux

Beckman

et al. 2019

Journal of Neurochemistry

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“…For example, Yang and colleagues 55 have proposed that BMMSC-derived Exos can prevent ovarian follicular atresia in cyclophosphamide (CTX)-treated rats via delivering miR-144-5p into ovarian cells, an effect is reversed by inhibition of miR-144-5p. Furthermore, systemic injection of miR-133b containing Exos preserves neurons, promotes axon regeneration, and improves the recovery of hindlimb locomotor function following spinal cord injury 56 . Actually, miR-133b regulates the transcriptional activator, Pitx3, an important factor in dopaminergic neurons development 57 and is downregulated in PD patients.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy

et al. 2020

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Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.

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“…[28] Besides, injection of miR-133b exosomes produces effects in neuron protection, promotion of the axon regeneration, and enhancement of the damaged locomotor function caused by SCI. [29] In light of the previous results, the delivery of siRNA/miRNA by exosomes is assumed to be an effective therapeutic strategy for neuron diseases. In this study, we engineered an exosome vector containing Lamp2b in HEK293T cells with the results hinted that the transfer of either exosome-mediated miRNAs or siRNAs represented a novel therapeutic approach for the treatment of SCI.…”

Section: Discussionmentioning

confidence: 99%

Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

Liao¹,

Ming²,

Guo³

2020

Preprint

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Background: As exosomes have been confirmed as a reservoir of siRNAs involved in certain diseases, the current study aims to investigate whether exosomal-siRNA could exert a protective role in spinal cord injury (SCI). Methods and Results: Exosomes in our experiment were isolated from lysosomal membrane-associated protein 2b (Lamp2b) overexpression HEK 293T cells, and purity of exosomes was characterized by the expression of CD9, CD47, and CD63 via western blot. Furthermore, the siRNA pool contains four siRNAs including siRNA-NgR, siRNA-LINGO-1, siRNA-Troy, and siRNA-PTEN was loaded to the exosomes, which indicated a significant role for the siRNA pool in reducing the expression of axon growth inhibitory factors. Upon the completion of loading into exosomes (exo-siRNA pool), the exo-siRNA pool was injected into primary cortical neurons of the SCI model in rats before cell proliferation and Rho expression were determined With the results revealed that purified addition could be applied to future experiments. The exo-siRNA pooled transfection caused downregulation of axon growth suppressors in primary cortical neurons including Nogo receptors (NgR), leucine-rich repeats and immunoglobulin domain-containing protein 1 (LINGO-1), Troy, and phosphatase and tenson homolog (PTEN). Cell proliferation and Rho expression of primary cortical neurons inhibited the expression of axonal growth inhibitors in rats with SCI by transfecting exogenous Sirna. Conclusion: This study confirmed that exosomes derived from Lamp2b overexpression HEK 293T cells facilitated both the recovery of functions and the survival of neurons when being loaded with the siRNA pool.

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Exosomes Derived From miR-133b-Modified Mesenchymal Stem Cells Promote Recovery After Spinal Cord Injury

Cited by 138 publications

References 54 publications

Construction and reconstruction of brain circuits: normal and pathological axon guidance

Construction and reconstruction of brain circuits: normal and pathological axon guidance

Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy

Exosome-Mediated siRNA pool Inhibits Axonal Growth Inhibitor in Cortical Neurons of Spinal Cord Injury in Rats

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