Evidence map›Paper›PMID 35922863›Full record

ArticleStem cell research & therapy2022

Mesenchymal stem cell-derived extracellular vesicles protect retina in a mouse model of retinitis pigmentosa by anti-inflammation through miR-146a-Nr4a3 axis.

Jia Zhang, Pengdong Li, Guifang Zhao, Siqi He, Di Xu, Weijie Jiang, Qian Peng, Zhaohui Li, Zhongjian Xie, Han Zhang and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 7 institutions in 1 country.

Jia Zhang *The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Pengdong Li *The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Guifang ZhaoThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Siqi HeThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Di XuGuangdong-Hong Kong-Macau Institute of Central Nervous System Regeneration, Key Laboratory of Central Nervous System Regeneration, Ministry of Education, Jinan University, Guangzhou, 510632, China.
Weijie JiangThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Qian PengThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Zhaohui LiThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Zhongjian XieInstitute of Pediatrics, Shenzhen Children's Hospital, Shenzhen, 518038, China.
Han ZhangThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China.
Ying XuGuangdong-Hong Kong-Macau Institute of Central Nervous System Regeneration, Key Laboratory of Central Nervous System Regeneration, Ministry of Education, Jinan University, Guangzhou, 510632, China. xuying@jnu.edu.cn.
Ling QiThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, B24 Yinquan South Road, Qingyuan, 511518, Guangdong, China. qiling1718@gzhmu.edu.cn.ORCID 0000-0002-7857-5969
Guangzhou Medical University · CNJinan University · CNBeihua University · CNGannan Medical University · CNJilin University · CNShenzhen Children's Hospital · CNShenzhen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRetinitis pigmentosa is a rod-cone degenerative disease that induces irreversible vision loss. This study probed the protective capacity of mesenchymal stem cell-derived small EVs (MSC-EVs) on the retinas of rd10 mice and the underlying mechanism.

methodsMSC-EVs were injected into the vitreous of rd10 mice at postnatal day 14 and P21; morphology and function were examined at P28. The mechanism of action was explored by using co-culture of photoreceptor cell line 661 W and microglia cell line BV2.

resultsTreatment with MSC-EVs increased the survival of photoreceptors and preserved their structure. Visual function, as reflected by optomotor and electroretinogram responses, was significantly enhanced in MSC-EVs-treated rd10 mice. Mechanistically, staining for Iba1, GFAP, F4/80, CD68 and CD206 showed that MSC-EVs suppressed the activation of microglial, Müller glial and macrophages. Furthermore, western blotting showed that the treatment inhibited the NF-κB pathway. RNA-seq and qPCR showed that MSC-EVs upregulated anti-inflammatory cytokines while downregulating pro-inflammatory cytokines. MSC-EVs application in vitro decreased the number of TUNEL-positive 661 W cells co-cultured with LPS-stimulated BV2, with similar impact on the cytokine expression as in vivo study. Genetic screening predicted miR-146a to be the downstream target of MSC-EVs, which was detected in MSC-EVs and upregulated in co-cultured 661 W cells and BV2 cells after MSC-EVs treatment. Upregulation of miR-146a by using its mimic decreased the expression of the transcription factor Nr4a3, and its downregulation inhibition promoted Nr4a3 expression in both 661 W and BV2 cells. Nr4a3 was further identified as the target gene of miR-146a by dual-luciferase assay. Furthermore, overexpressing miR-146a significantly decreased the expression of LPS-induced pro-inflammatory cytokines in BV2 cells.

conclusionsMSC-EVs delays retinal degeneration in rd10 mice mainly by its anti-inflammatory effect via the miR-146a-Nr4a3axis. Hence, MSC-EVs may be used in the treatment of neurodegenerative diseases.

Indexed as

Extracellular VesiclesMesenchymal Stem CellsMicroRNAsReceptors, SteroidRetinitis PigmentosaAnimalsAnti-Inflammatory AgentsCytokinesDisease Models, AnimalDNA-Binding ProteinsLipopolysaccharidesMiceNerve Tissue ProteinsReceptors, Thyroid HormoneRetinaAnti-Inflammatory AgentsCytokinesDNA-Binding ProteinsLipopolysaccharidesMicroRNAsNerve Tissue ProteinsNr4a3 protein, mouseReceptors, SteroidReceptors, Thyroid HormoneExtracellular vesiclesInflammationmiR-146a-Nr4a3 axisrd10 mouseRetinitis pigmentosa

Identifiers

PMID35922863
PMCPMC9351183
OpenAlexW4289550227

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.