Combinational Treatment of Bioscaffolds and Extracellular Vesicles in Spinal Cord Injury

Wang, Xizhi; Botchway, Benson O. A.; Zhang, Yong; Yuan, Jiaying; Liu, Xuehong

doi:10.3389/fnmol.2019.00081

Cited by 28 publications

(17 citation statements)

References 117 publications

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“…Exosomes are thought to mediate a novel mechanism of cell-to-cell communication [ 19 , 20 ]. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles, which were beneficial for SCI [ 21 – 23 ]. Exosomes are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes

et al. 2020

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Background: Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. Methods: A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray analysis and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. Results: The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. Conclusion: A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI.

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Section: Introductionmentioning

confidence: 99%

Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes

et al. 2020

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“…However, BMSCs transplantation also has some drawbacks, such as teratogenic tumorigenesis, immune rejection, pulmonary embolism, low transplantation rate, and survival rate (5,6). Exosomes (diameter: 30-100 nm) are extracellular vesicles released from cells into the extracellular space (7). As an important mediator of cell-cell interaction, exosomes can enter target cells through membrane receptors or endocytosis, and then participate in the regulation of biological information via transmitting mRNAs, non-coding small RNAs, proteins, etc.…”

Section: Introductionmentioning

confidence: 99%

“…(8). Noteworthy, exosomes exert positive therapeutic effects on SCI through inhibiting neuronal apoptosis and inflammatory response (7). Huang et al (9) found that the administration of mesenchymal stem cells (MSCs)-derived exosomes in SCI rats significantly attenuates the lesion size, as well as cellular apoptosis and inflammation in the injured spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Exosomes secreted from miRNA-29b-modified mesenchymal stem cells repaired spinal cord injury in rats

Zhao

Shou-zhi

et al. 2019

Braz J Med Biol Res

107

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Exosomes, a kind of extracellular vesicle, are promising therapeutic agents for spinal cord injury (SCI). This article aimed to investigate effects of exosomes secreted from miRNA-29b-modified bone marrow mesenchymal stem cells (BMSCs) on SCI. Exosomes were extracted from BMSCs transfected with miRNA-29b or negative control (miR NC). SCI rats were injected intravenously with exosomes (control exosomes, miRNA-29b exosomes) and BMSCs (miR NC, miRNA-29b) through the tail vein. The expression of miRNA-29b in spinal cord tissues of SCI rats was detected by qRT-PCR. The hind limb motor function was evaluated by Basso Beattie Bresnahan (BBB) score. The histopathological damage and neuronal regeneration in spinal cord tissues was observed by HE staining and immunohistochemistry, respectively. The injection of miRNA-29b exosomes and miRNA-29b BMSCs both significantly increased the expression of miRNA-29b in spinal cord tissues of SCI rats (P<0.05). Compared with SCI rats, rats in the miRNA-29b exosomes and the miRNA-29b groups exhibited improved SCI, including increased BBB score, NF200 and GAP-43 positive neurons, as well as decreased contractile nerve cell numbers and GFAP positive neurons (all P<0.05). The relieving degree of SCI was significantly higher in the miRNA-29b exosomes group than in the miRNA-29b BMSCs group (P<0.05). Exosomes secreted from miRNA-29b-modified BMSCs were effective in the repair of SCI in rats.

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“…Exosomes derived from MSCs are easier to obtain and store and are subject to little ethical restriction compared with MSCs [63]. The volume of exosomes is significantly smaller than that of MSCs, so they will not be captured by lung and liver tissues, and they can penetrate the BSCB [64]. Therefore, attention has recently focused on the use of exosomes to treat SCI (Table 1).…”

Section: Treating Sci With Exosomes Derived From Mscsmentioning

confidence: 99%

Mesenchymal stem cell-derived exosomes: therapeutic opportunities and challenges for spinal cord injury

Liu

et al. 2021

Stem Cell Res Ther

139

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Spinal cord injury (SCI) often leads to serious motor and sensory dysfunction of the limbs below the injured segment. SCI not only results in physical and psychological harm to patients but can also cause a huge economic burden on their families and society. As there is no effective treatment method, the prevention, treatment, and rehabilitation of patients with SCI have become urgent problems to be solved. In recent years, mesenchymal stem cells (MSCs) have attracted more attention in the treatment of SCI. Although MSC therapy can reduce injured volume and promote axonal regeneration, its application is limited by tumorigenicity, a low survival rate, and immune rejection. Accumulating literature shows that exosomes have great potential in the treatment of SCI. In this review, we summarize the existing MSC-derived exosome studies on SCI and discuss the advantages and challenges of treating SCI based on exosomes derived from MSCs.

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Combinational Treatment of Bioscaffolds and Extracellular Vesicles in Spinal Cord Injury

Cited by 28 publications

References 117 publications

Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes

Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes

Exosomes secreted from miRNA-29b-modified mesenchymal stem cells repaired spinal cord injury in rats

Mesenchymal stem cell-derived exosomes: therapeutic opportunities and challenges for spinal cord injury

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