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

Yu, Tao; Zhao, Cunju; Shou-zhi, Hou; Zhou, Weijie; Wang, Baoxin; Chen, Yunzhen

doi:10.1590/1414-431x20198735

Cited by 94 publications

(61 citation statements)

References 36 publications

(39 reference statements)

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“…Therefore, their secreted exosomes can be good candidates for therapeutic purpose [ 16 ]. An example is bone marrow derived MSC transfected with miR-29b for healing injured spinal cord in rats via exosomes encapsulated miR-29b [ 18 ].…”

Section: Progress In Mirna-enriched Ev Therapiesmentioning

confidence: 99%

Therapeutic miRNA-Enriched Extracellular Vesicles: Current Approaches and Future Prospects

Munir

Yoon

Ryu

2020

Cells

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Extracellular vesicles (EVs) are 50–300 nm vesicles secreted by eukaryotic cells. They can carry cargo (including miRNA) from the donor cell to the recipient cell. miRNAs in EVs can change the translational profile of the recipient cell and modulate cellular morphology. This endogenous mechanism has attracted the attention of the drug-delivery community in the last few years. EVs can be enriched with exogenous therapeutic miRNAs and used for treatment of diseases by targeting pathological recipient cells. However, there are some obstacles that need to be addressed before introducing therapeutic miRNA-enriched EVs in clinics. Here, we focused on the progress in the field of therapeutic miRNA enriched EVs, highlighted important areas where research is needed, and discussed the potential to use them as therapeutic miRNA carriers in the future.

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Section: Progress In Mirna-enriched Ev Therapiesmentioning

confidence: 99%

Therapeutic miRNA-Enriched Extracellular Vesicles: Current Approaches and Future Prospects

Munir

Yoon

Ryu

2020

Cells

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“…[26] Reports have revealed that rehabilitation of SCI rats achieved satisfactory results via injecting intravenously with exosomes (control exosomes, miRNA-29b exosomes) and BMSCs (miR NC, miRNA-29b) to the tail vein. [27] Li has suggested that exosomes derived from miR-544 modi ed BMSCs exhibited a protective role for the SCI rat model in improving their functional recovery as well as the promotion of neuronal survival. [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.…”

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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“…Treatment with miR-133b-rich EVs promoted the recovery of hindlimb locomotor function, reduced the lesion volume, protected the neuronal cells and enhanced axon regeneration compared to the EV and control groups. MSCs-derived exosomes also have been modified to transfer miR-29b and miR-216a-5p to promote regeneration of injured spinal cord [ 88 , 89 ]. Interestingly, MSCs-derived exosomes also have been used to deliver phosphatase and tensin homology small interfering RNA (PTEN) that promote neuronal cell growth, support angiogenesis and suppressing gliosis when the exosomes were delivered intranasally to the rat SCI model [ 79 ].…”

Section: Novel Biological Therapies For Spinal Cord Injurymentioning

confidence: 99%

Treatment of spinal cord injury with mesenchymal stem cells

Liau

Looi²,

Chia³

et al. 2020

Cell Biosci

123

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Background Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life. Results This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue. Conclusion These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

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

Cited by 94 publications

References 36 publications

Therapeutic miRNA-Enriched Extracellular Vesicles: Current Approaches and Future Prospects

Therapeutic miRNA-Enriched Extracellular Vesicles: Current Approaches and Future Prospects

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

Treatment of spinal cord injury with mesenchymal stem cells

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