Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury

Li, Chenggang; Xiao, Li; Zhao, Bichun; Wang, Chunfang

doi:10.1080/13813455.2019.1691601

Cited by 68 publications

(51 citation statements)

References 12 publications

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“…The function of miR-544 in the central nervous system has been widely studied [40][41][42] . The expression of miR-544a was downregulated after spinal cord injury in mice and overexpression of miR-544a alleviated neuroinflammation in the spinal cord and restored motor function 42 .…”

Section: Discussionmentioning

confidence: 99%

miR-544-3p mediates arthritis pain through regulation of FcγRI

Liu

Jeon

2021

Preprint

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Chronic or episodic joint pain is a major symptom in rheumatoid arthritis (RA) and its adequate treatment represents an unmet medical need. However, the cellular and molecular mechanisms underlying RA pain remain elusive. Non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of RA as negative regulators of the stability or translation of specific target mRNAs. Yet, their significance in RA pain is still not well defined. We and other groups recently identified neuronally expressed FcγRI as a key driver of arthritis pain in mouse RA models. Thus, we tested the hypothesis that miRNAs that target and regulate neuronal FcγRI attenuate RA pain. Here, we show that miR-544-3p was robustly downregulated whereas FcγRI was significantly upregulated in the dorsal root ganglion (DRG) in mouse RA models. Intrathecal injection of miR-544-3p mimic attenuated established mechanical and heat hyperalgesia in a mouse model of collagen II-induced arthritis (CIA). Moreover, this effect was likely mediated, at least in part, by FcγRI since miR-544-3p mimic downregulated FcγRI in the DRG during arthritis and genetic deletion of FcγRI produced similar antihyperalgesic effects in the CIA model. This notion was further supported by a dual luciferase assay showing that miR-544-3p targeted FcγRI by directly binding to its 3’UTR. In addition, FcγRI expression in DRG neurons in vitro was downregulated by miR-544-3p mimic and upregulated by miR-544-3p inhibitor. In naïve mice, miR-544-3p mimic alleviated acute joint pain hypersensitivity induced by IgG immune complex (IgG-IC), whereas miR-544-3p inhibitor potentiated the pro-nociceptive behavioral effect of IgG-IC. These findings suggest that miR-544-3p causally participates in the maintenance of arthritis pain by targeting neuronal FcγRI, and thus define miR-544-3p as a new potential therapeutic target for treating RA pain.

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Section: Discussionmentioning

confidence: 99%

miR-544-3p mediates arthritis pain through regulation of FcγRI

Liu

Jeon

2021

Preprint

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“…[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. [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.…”

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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“…Another exosomal miRNA that has neuroprotective effects is miRNA-544. Li et al [151] transfected rat BMSCs with miRNA-544 mimic to obtain exosomes that highly expressed miRNA-544 and these exosomes were intravenously injected into a SCI rat model. The results showed that miRNA-544 accelerates the recovery of neuronal function after SCI.…”

Section: Other Mirnas Of Exosomes Derived From Mscs In Scimentioning

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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Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury

Cited by 68 publications

References 12 publications

miR-544-3p mediates arthritis pain through regulation of FcγRI

miR-544-3p mediates arthritis pain through regulation of FcγRI

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

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

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