Evidence map›Paper›PMID 37798761›Full record

ArticleInflammation and regeneration2023

Placenta mesenchymal stem cell-derived extracellular vesicles alleviate liver fibrosis by inactivating hepatic stellate cells through a miR-378c/SKP2 axis.

Wenjie Zheng, Saiyan Bian, Shi Qiu, Colin E Bishop, Meimei Wan, Nuo Xu, Xieyin Sun, Russel Clive Sequeira, Anthony Atala, Zhifeng Gu and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammation and regeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

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  12. Extracellular vesicles: emerging therapeutic agents for liver fibrosis.Extracellular vesicles and circulating nucleic acids · 2025
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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.

Wenjie Zheng *Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China. wenjiezheng@ntu.edu.cn.ORCID http://orcid.org/0000-0001-5987-5272
Saiyan Bian *Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Shi Qiu *Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Colin E BishopWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
Meimei WanResearch Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Nuo XuResearch Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Xieyin SunResearch Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Russel Clive SequeiraWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
Anthony AtalaWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
Zhifeng GuResearch Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China. guzhifeng@126.com.
Weixin ZhaoWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC, 27157, USA. wezhao@wakehealth.edu.

Funding

Jiangsu Provincial Key Research and Development Program BE2020668National Natural Science Foundation of China 81702419National Natural Science Foundation of China 82070622National Natural Science Foundation of China 82272839
6 · The paper itself

Abstract

backgroundExtracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) have shown therapeutic effects on liver fibrosis. This study aimed to evaluate the effects of extracellular vesicles from placenta-derived MSCs (Pd-MSCs-EVs) on liver fibrosis at 3D/2D levels and explore the potential mechanisms.

methodsThe multicellular liver organoids, consisting of hepatocytes, hepatic stellate cells (HSCs), Kupffer cells, and liver sinusoidal endothelial cells, were observed for growth status, morphological changes, and metabolism. Human transformation growth factor- beta 1 (TGF-β1) was used to induce fibrosis at optimal concentration. The anti-fibrosis effects of Pd-MSCs-EVs were evaluated in liver organoids and HSCs models. Anti-fibrotic content of Pd-MSCs-EVs was identified by multiple experimental validations.

resultsTGF-β1 induced fibrosis in liver organoids, while Pd-MSCs-EVs significantly alleviated fibrotic phenotypes. Following serial verifications, miR-378c was identified as a potential key anti-fibrosis content. In contrast, miR-378c depletion decreased the anti-fibrotic effects of Pd-MSCs-EVs. Additionally, Pd-MSCs-EVs administration repressed TGF-β1-mediated HSCs activation at 2D or 3D levels. Mechanistically, exosomal miR-378c inactivated HSCs by inhibiting epithelial-mesenchymal transition (EMT) through stabilizing E-cadherin via targeting its E3 ubiquitin ligase S-Phase Kinase Associated Protein 2 (SKP2).

conclusionPd-MSCs-EVs ameliorated TGF-β1-induced fibrosis by deactivating HSCs in a miR-378c/SKP2-dependent manner, which may be an efficient therapeutic candidate for liver fibrosis.

Indexed as

Extracellular vesiclesLiver fibrosisMesenchymal stem/stromal cellsmiR-378cMulticellular organoids

Identifiers

PMID37798761
PMCPMC10557276

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Registered trials

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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.