Mesenchymal stem cell-derived exosomes containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway

Jiang, Zhensong; Zhang, Jianru

doi:10.1080/15384101.2021.1919825

Cited by 63 publications

(49 citation statements)

References 43 publications

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“…The process of study selection is outlined in Figure 1 . A total of 153 articles were identified, of which 11 articles satisfied the inclusion criteria ( Ji et al, 2019 ; Kang et al, 2019 ; Yu et al, 2019 ; Kang et al, 2020 ; Liu et al, 2020 ; Wang et al, 2020 ; Jia et al, 2021 ; Jiang and Zhang, 2021 ; Zhang L. et al, 2021 ). After deleting duplicate articles, we excluded 74 irrelevant articles (e.g., irrelevant disease models, reviews, and conferences) by examining the title and abstract of the article.…”

Section: Resultsmentioning

confidence: 99%

“…Several studies reported intravenous administration of the same dose of exosomes (100 μg, 200 µg). The studies used many different miRNAs to modify exosomes, including miR-26a ( Chen et al, 2021 ), miR-126 ( Huang et al, 2020 ), miR-145-5p ( Jiang and Zhang, 2021 ), miR-381 ( Jia et al, 2021 ), miR-21 ( Ji et al, 2019 ; Kang et al, 2019 ), miR-216a-5p ( Liu et al, 2020 ), miR-421-3p ( Wang et al, 2020 ), miR-29b ( Yu et al, 2019 ) and miR-181c ( Zhang M. et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

Cao

Jiang

2022

Front. Bioeng. Biotechnol.

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Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI.Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis.Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39–5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE’s ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment.Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

Cao

Jiang

2022

Front. Bioeng. Biotechnol.

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“…Among the included 32 studies, only two studies were controlled studies ( 29 , 33 ), and the remaining 30 studies were randomized controlled studies. The species of animals included SD rats ( 19 – 21 , 28 – 37 , 39 , 40 , 42 – 44 , 46 , 47 , 49 – 53 , 55 , 56 ), Wistar rats ( 41 , 54 ), and C57BL/6 mice ( 38 , 45 , 48 ); gender included male ( 28 , 30 – 32 , 38 – 45 , 49 , 53 , 54 ) and female ( 19 , 20 , 29 , 33 , 34 , 36 , 37 , 46 – 48 , 50 – 52 , 55 , 56 ), two studies did not report the sex of the animals ( 21 , 35 ); the weights of animals were between 150 ( 41 ) and 300 g ( 20 , 44 ), the weight of the mouse was between 17 and 22 g ( 48 ), and seven of the studies did not report the weight of the animals ( 21 , 29 , 30 , 38 , 42 , 45 , 50 ); age was between 6 ( 38 , 44 , 45 , 50 , 51 ) and 12 weeks ( 47 , 56 ), and nine of the studies did not report the age of the animals ( …”

Section: Resultsmentioning

confidence: 99%

“…Six studies reported types of exosomes but did not report specific sources ( 31 , 32 , 38 , 40 , 45 , 46 ). The transplantation route of exosomes included tail vein ( 19 – 21 , 29 – 32 , 34 – 50 , 52 – 56 ), intranasally ( 33 ) and subcutaneous ( 51 ), and one study did not report the route of exosome transplantation ( 28 ); the time transplantation of exosome ranged from 0 ( 19 , 20 , 31 , 38 , 41 , 44 – 47 , 49 ) to 24 h ( 42 , 43 ) after modeling, one study did not report the time of exosome transplantation ( 40 ); dose of exosomes ranged from 20 ( 29 ) to 200 μg ( 28 , 30 – 33 , 36 – 38 , 41 , 43 , 45 – 49 , 53 , 56 ); the control group includes PBS ( 19 – 21 , 28 – 32 , 34 , 35 , 38 , 39 , 41 , 43 – 51 , 53 – 56 ), saline ( 33 , 36 , 37 , 40 , 42 ), and blank ( 52 ). Basic information of the study subjects was summarized in Supplementary Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Effect of Exosomes Derived From Stem Cells in Spinal Cord Injury: A Systematic Review Based on Animal Studies

et al. 2022

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ObjectiveA systematic review of the role of stem cell-derived exosomes in repairing spinal cord injury (SCI) and the existing problems in animal experiments to provide a reference for better animal experiments and clinical studies in the future.MethodThree electronic databases, namely PubMed, Web of Science, and Ovid-Embase were searched. The studies were retrieved from inception to October 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria.Results and DiscussionThirty-two studies were incorporated into the final analyses. Exosomes derived from stem cells could not only significantly improve the motor function of animals with SCI, but also significantly increase the expression of anti-inflammatory factors IL-4 and IL-10 and anti-apoptotic protein Bcl-2, while significantly lowering the pro-inflammatory factor IL-1β and TNF-α and the expression of the apoptotic protein BAX. However, the mechanism of exosome-mediated SCI repair, as well as the best source and dosage remain unknown. In addition, there are still some issues with the design, implementation, and reporting of animal experiments in the included studies. Therefore, future research should further standardize the implementation and reporting of animal studies and fully explore the best strategies for exosomes to repair SCI so as to promote the translation of preclinical research results to clinical research better and faster.

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“…Finally, Sun et al demonstrated that the sub-acute co-transplantation of human NSC and MSC enhanced stem cell survival compared to individual treatments, increased the number of myelinated axons, and improved locomotor function [ 52 ]. The use of MSC secretome, alone or in combination with NSC, would provide a successful alternative to cell therapy, since researchers have ascribed paracrine effects to exosomes in the treatment of spinal cord injuries including anti-inflammatory [ 53 ], angiogenic [ 54 ] and regenerative effects [ 55 ], as well as functional recovery [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

Bonilla

Hernández

Giraldo

et al. 2021

IJMS

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We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.

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Mesenchymal stem cell-derived exosomes containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway

Cited by 63 publications

References 43 publications

The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

Therapeutic Effect of Exosomes Derived From Stem Cells in Spinal Cord Injury: A Systematic Review Based on Animal Studies

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

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