Evidence map›Paper›PMID 37095581›Full record

ArticleStem cell research & therapy2023

TNF-α/IL-1β-licensed hADSCs alleviate cholestatic liver injury and fibrosis in mice via COX-2/PGE2 pathway.

Xiaoyu Luan, Peng Chen, Yaxin Li, Xinying Yuan, Longyu Miao, Pengyu Zhang, Qilong Cao, Xiaomin Song, Guohu Di

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

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  11. Exploring the Potential Mechanisms of Action ofCombinatorial chemistry & high throughput screening · 2024
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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

9 authors at 2 institutions in 1 country.

Xiaoyu Luan *School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Peng Chen *School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Yaxin LiSchool of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Xinying YuanSchool of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Longyu MiaoSchool of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Pengyu ZhangSchool of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Qilong CaoQingdao Haier Biotech Co. Ltd, Qingdao, China.
Xiaomin SongSchool of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
Guohu DiSchool of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China. diguohu@qdu.edu.cn.ORCID 0000-0001-9940-730X
Qingdao University · CNHaier Group (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdipose tissue-derived stem cell (ADSC) transplantation has been shown to be effective for the management of severe liver disorders. Preactivation of ADSCs enhanced their therapeutic efficacy. However, these effects have not yet been examined in relation to cholestatic liver injury.

methodsIn the present study, a cholestatic liver injury model was established by bile duct ligation (BDL) in male C57BL/6 mice. Human ADSCs (hADSCs) with or without tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) pretreatment were administrated into the mice via tail vein injections. The efficacy of hADSCs on BDL-induced liver injury was assessed by histological staining, real-time quantitative PCR (RT-qPCR), Western blot, and enzyme-linked immune sorbent assay (ELISA). In vitro, the effects of hADSC conditioned medium on the activation of hepatic stellate cells (HSCs) were investigated. Small interfering RNA (siRNA) was used to knock down cyclooxygenase-2 (COX-2) in hADSCs.

resultsTNF-α/IL-1β preconditioning could downregulate immunogenic gene expression and enhance the engraftment efficiency of hADSCs. Compared to control hADSCs (C-hADSCs), TNF-α/IL-1β-pretreated hADSCs (P-hADSCs) significantly alleviated BDL-induced liver injury, as demonstrated by reduced hepatic cell death, attenuated infiltration of Ly6G + neutrophils, and decreased expression of pro-inflammatory cytokines TNF-α, IL-1β, C-X-C motif chemokine ligand 1 (CXCL1), and C-X-C motif chemokine ligand 2 (CXCL2). Moreover, P-hADSCs significantly delayed the development of BDL-induced liver fibrosis. In vitro, conditioned medium from P-hADSCs significantly inhibited HSC activation compared to that from C-hADSCs. Mechanistically, TNF-α/IL-1β upregulated COX-2 expression and increased prostaglandin E2 (PGE2) secretion. The blockage of COX-2 by siRNA transfection reversed the benefits of P-hADSCs for PGE2 production, HSC activation, and liver fibrosis progression.

conclusionIn conclusion, our results suggest that TNF-α/IL-1β pretreatment enhances the efficacy of hADSCs in mice with cholestatic liver injury, partially through the COX-2/PGE2 pathway.

Indexed as

Chemical and Drug Induced Liver Injury, ChronicCholestasisAnimalsChemokinesCulture Media, ConditionedCyclooxygenase 2DinoprostoneFibrosisHumansLigandsLiverLiver CirrhosisMaleMiceMice, Inbred C57BLTumor Necrosis Factor-alphaChemokinesCulture Media, ConditionedCyclooxygenase 2DinoprostoneLigandsTumor Necrosis Factor-alphaAdipose tissue-derived stem cellsBile duct ligationCOX-2/PGE2 pathwayLiver fibrosisTNF-α/IL-1β pretreatment

Identifiers

PMID37095581
PMCPMC10127380
OpenAlexW4366823121

What OpenQuestion holds

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LicenceCC BY
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.