miR-21 deficiency contributes to the impaired protective effects of obese rat mesenchymal stem cell-derived exosomes against spinal cord injury

Ji, Wenchen; Jiang, Wanting; Li, Meng; Li, Jia; Li, Zhiqiang

doi:10.1016/j.biochi.2019.10.002

Cited by 46 publications

(27 citation statements)

References 40 publications

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“…In addition, miR-21-5p exerts an antiapoptotic effect that is also related to the decreased expression of FasL, which is a proapoptotic gene [110]. Of note, miR-21 deficiency in obese rats is caused by insulin resistance, and secreted MSC-exosomes have no significant effect on SCI rats [79]. The above results further prove that MSC-derived exosomes can alleviate SCI by inhibiting apoptosis.…”

Section: Msc-exosomes Inhibit Cell Apoptosismentioning

confidence: 89%

Mesenchymal Stem Cell-Derived Exosomes: Hope for Spinal Cord Injury Repair

Ren

Yao

Sun

et al. 2020

Stem Cells and Development

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Spinal cord injury (SCI) is a devastating medical condition with profound social and economic impacts. Although research is ongoing, current treatment options are limited and do little to restore functionality. However, recent studies suggest that mesenchymal stem cell-derived exosomes (MSC-exosomes) may hold the key to exciting new treatment options for SCI patients. MSCs are self-renewing multipotent stem cells with multi-directional differentiation and can secrete a large number of exosomes (vesicles secreted into the extracellular environment through endocytosis, called MSC-exosomes). These MSC-exosomes play a critical role in repairing SCI through promoting angiogenesis and axonal growth, regulating inflammation and the immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be utilized to transport genetic material or drugs to target cells, and their relatively small size makes them able to permeate the blood-brain barrier. In this review, we summarize recent advances in MSC-exosome themed SCI treatments and cell-free therapies to better understand this newly emerging methodology.

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Section: Msc-exosomes Inhibit Cell Apoptosismentioning

confidence: 89%

Mesenchymal Stem Cell-Derived Exosomes: Hope for Spinal Cord Injury Repair

Ren

Yao

Sun

et al. 2020

Stem Cells and Development

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“…These regulatory effects of lncRNAs have also begun to attract widespread attention 11 . Recent studies have shown that some lncRNAs are involved in regulating the adipose differentiation and osteogenic differentiation of BMSCs 12,13 . Studies have reported that LncRNA H19 can stimulate the osteogenic differentiation of BMSCs, while inhibiting the adipogenic differentiation of BMSCs 14,15 .…”

Section: Introductionmentioning

confidence: 99%

“…11 Recent studies have shown that some lncRNAs are involved in regulating the adipose differentiation and osteogenic differentiation of BMSCs. 12,13 Studies have reported that LncRNA H19 can stimulate the osteogenic differentiation of BMSCs, while inhibiting the adipogenic differentiation of BMSCs. 14,15 Our previous research results indicate that LncRNA H19 adsorbs miR-188 through the ceRNA mechanism and then mediates LCoR's influence on the osteogenic and adipogenic differentiation of mouse BMSCs, 15 but does LncRNA H19 pass externally?…”

Section: Introductionmentioning

confidence: 99%

Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

Wang

Chen

Zhao

et al. 2021

J Cellular Molecular Medi

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This study explored the therapeutic effect of bone marrow mesenchymal stem cell‐derived exosomes on the treatment of obesity‐induced fracture healing. Quantitative real‐time PCR was used to detect the expression of lncRNA H19, miR‐467 and Hoxa10 and combined with WB detection to detect osteogenic markers (RUNX2, OPN, OCN). Determine whether exosomes have entered BMSCs by immunofluorescence staining. Alkaline phosphatase (ALP) and alizarin red staining (ARS) staining were used to detect ALP activity and calcium deposition. We found that high‐fat treatment can inhibit the secretion of BMSCs‐derived exosomes and affect the expression of H19 carried by them. In vivo and in vitro experiments show that high‐fat or obesity factors can inhibit the expression of osteogenic markers and reduce the staining activity of ALP and ARS. The treatment of exosomes from normal sources can reverse the phenomenon of osteogenic differentiation and abnormal fracture healing. Further bioinformatics analysis found that miR‐467 as a regulatory molecule of lncRNA H19 and Hoxa10, and we verified the targeting relationship of the three through dual luciferase report experiments. Further, we found similar phenomena in ALP and ARS staining. Bone marrow mesenchymal stem cell‐derived exosomes improve fracture healing caused by obesity.

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“…A study Using exosomes from non-coding RNA ( miRNA-29b ) injected rats with spinal cord injury, the degree of spinal cord injury relief was signi cantly improved (14). There are also studies suggesting that the lack of certain non-coding RNA ( miR-21 ) may inhibit the protective effect of exosomes on the spinal cord (15). Non coding RNA is involved in the process of neuron death, demyelination, neuroglia cell, in ammatory reaction, so it has potential value in the treatment of SCI(16,17).…”

Section: Introductionmentioning

confidence: 99%

Identification Of Exosomal LncRNAs From Peripheral Blood In Spinal Cord Injury Mouse Model

Shi

Cong

et al. 2021

Preprint

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Background Spinal Cord Injury ( SCI ) is a disease leading to permanent neurological dysfunction. In recent years, exosomes and non-coding RNAs have been considered as potential therapeutic agents for spinal cord injury. Based on ceRNA regulatory network, the role of non-coding RNAs has been paid attention to, and some genes related to the pathological process after spinal cord injury have been found. However, most gene studies only focus on exosomes and non-coding RNAs in spinal cord injury sites, and few genes related to spinal cord injury repair have been found. Objective We aimed to identify exosomes and non-coding RNA in peripheral blood after spinal cord injury, and to predict its role in spinal cord injury according to gene expression profiles. Materials and methods After successful modeling of spinal cord injury, rat exosomes were extracted from peripheral blood.Western-Blot was used to identify exosomes. After RNA was extracted from exosomes, total transcriptome sequencing and differential gene GO and KEGG Pathway analysis were performed. We selected potential genes for quantitative Real-Time PCR (qRT-PCR) assays and predicted their potential regulatory networks. Results The successful establishment of spinal cord injury model was confirmed by Tarlov’s scores, and the extracted exosomes were confirmed by Western-Blot and electron microscopy. Among the significantly differentially expressed lncRNAs, XR_351404, XR_353833, XR_590719, XR_590076, and XR_591455 were associated with miRNA related to repair after spinal cord injury. Conclusions The regulatory effect of this network may play a key role in the repair process of SCI. The differential lncRNAs we found may serve as therapeutic targets and diagnostic biomarkers for SCI.

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miR-21 deficiency contributes to the impaired protective effects of obese rat mesenchymal stem cell-derived exosomes against spinal cord injury

Cited by 46 publications

References 40 publications

Mesenchymal Stem Cell-Derived Exosomes: Hope for Spinal Cord Injury Repair

Mesenchymal Stem Cell-Derived Exosomes: Hope for Spinal Cord Injury Repair

Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

Identification Of Exosomal LncRNAs From Peripheral Blood In Spinal Cord Injury Mouse Model

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