Evidence map›Paper›PMID 39490995›Full record

ArticleStem cell research & therapy2024

Mesenchymal stromal cells alleviate APAP-induced liver injury via extracellular vesicle-mediated regulation of the miR-186-5p/CXCL1 axis.

Erming Zhao, Rukang Liang, Panlong Li, Di Lu, Shuhan Chen, Weikeng Tan, Yunfei Qin, Yana Zhang, Yingcai Zhang, Qi Zhang and 1 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
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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

11 authors.

Erming Zhao *Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Rukang Liang *Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Panlong Li *Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Di LuBiotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Shuhan ChenBiotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Weikeng TanBiotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Yunfei QinBiotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Yana ZhangDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
Yingcai ZhangDepartment of Hepatic Surgery and Liver Transplantation Centre, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China. zhangyc3@mail.sysu.edu.cn.
Qi ZhangBiotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China. zhangq27@mail.sysu.edu.cn.
Qiuli LiuBiotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China. liuqli3@mail.sysu.edu.cn.ORCID 0000-0002-8090-8718

Funding

the National Natural Science Foundation of China 81971526 and 82370629the Natural Science Foundation of Guangdong Province 2022A1515012223the Science and Technology Program of Guangzhou 202201020398, 202201020430
6 · The paper itself

Abstract

backgroundAcetaminophen (APAP) overdose is a significant cause of drug-induced liver injury (DILI). N-acetylcysteine (NAC) is the first-line agent used in the clinic. However, it rarely benefits patients with advanced APAP toxicity. Mesenchymal stromal cells (MSCs) have demonstrated potential in treating DILI. However, the specific mechanism by which MSCs protect against APAP-induced liver injury remains unclear.

methodsAPAP was injected intraperitoneally to induce a liver injury model. We then detected histopathology, biochemical indices, and inflammatory cytokine levels to assess the efficacy of MSCs and MSC extracellular vesicles (MSC-EVs). Flow cytometry was performed to reveal the immunoregulatory effects of MSCs and MSC-EVs on the neutrophils. RNA sequencing (RNA-Seq) of liver tissues was used to identify critical target genes for MSC treatment.

resultsMSC and MSC-EV treatment effectively alleviated APAP-induced liver injury and inhibited neutrophil infiltration. RNA-Seq analysis and ELISA data indicated that C-X-C motif chemokine 1 (CXCL1), a chemoattractant for neutrophils, was a key molecule in the MSC-mediated amelioration of APAP-induced liver damage. In addition, neutralization of CXCL1 reduced APAP-induced liver damage, which was accompanied by decreased neutrophil infiltration. Importantly, we verified that MSC-EV-derived miR-186-5p directly binds to the 3'-UTR of Cxcl1 to inhibit its expression in hepatocytes. The agomir miR-186-5p showed excellent potential for the treatment of DILI.

conclusionsOur findings suggest that MSCs and MSC-EVs are an effective approach to mitigate DILI. Targeting the miR-186-5p/CXCL1 axis is a promising approach to improve the efficacy of MSCs and MSC-EVs in the treatment of DILI.

Indexed as

AcetaminophenChemical and Drug Induced Liver InjuryChemokine CXCL1Extracellular VesiclesMesenchymal Stem CellsMicroRNAsAnimalsHumansMaleMesenchymal Stem Cell TransplantationMiceMice, Inbred C57BLAcetaminophenChemokine CXCL1Cxcl1 protein, mouseMicroRNAsMIRN186 microRNA, humanCXCL1Extracellular vesiclesLiver injuryMesenchymal stromal cellsmiR-186-5pNeutrophils

Identifiers

PMID39490995
PMCPMC11533353

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.