Evidence map›Paper›PMID 41276869›Full record

ArticleStem cell research & therapy2025

Adipose-derived mesenchymal stem cell therapy modulates mitochondrial function to attenuate acetaminophen-induced liver injury by DDIT4/PGC-1α axis.

Yelei Cen, Caixia Xia, Shouhan Yao, Xinyu Weng, Jinjin Qi, Guohua Lou, Min Zheng, Yanning Liu

Abstract read
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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Yelei Cen *State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China.
Caixia Xia *State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China.
Shouhan Yao *State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China.
Xinyu WengState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China.
Jinjin QiState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China.
Guohua LouState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China. louguohua@zju.edu.cn.
Min ZhengState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China. minzheng@zju.edu.cn.
Yanning LiuState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China. liuyanning@zju.edu.cn.

Funding

Independent Task of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases zz202314National Key Research and Development Program of China 2023YFC2306800National Natural Science Foundation of China 82270624National Natural Science Foundation of China 82370613National Natural Science Foundation of China U24A20773
6 · The paper itself

Abstract

backgroundAcetaminophen (APAP) overdose is a leading cause of drug-induced liver injury, with limited treatment options. Mitochondrial dysfunction plays a central role in the pathogenesis of APAP-induced liver injury (AILI). Mitochondrial damage induces cell death, liver necrosis, and sever inflammation, leading to irreversible liver failure. Therefore, it is urgent to develop alternative treatments. Mesenchymal stem cell (MSC)-based cell therapy recently has received increasing attention for its role in regulating mitochondrial function.

objectiveThis study aimed to investigate the regulation of mitochondrial function and the therapeutic potential of MSCs in treating AILI and underlying mechanisms.

methodsAILI mouse model was established by injection of overdosed APAP. Mice were treated with adipose-derived MSCs (AMSCs) via the tail vein. The blood and liver tissues were collected for assessment of liver necrosis and mitochondrial function. To further verify the mechanism, hepatocyte-specific DNA damage-inducible transcript 4 (DDIT4) knockout (Ddit4

resultsWe showed that AMSCs treatment significantly reduced liver necrosis, oxidative stress, and mitochondrial dysfunction in AILI. DDIT4 expression in hepatocytes was identified as playing an important part in AMSCs treating AILI by using RNA-Seq and histological analysis. DDIT4 upregulation in liver samples of AILI patients characterized by snRNA-Seq and spatial transcriptomics analysis, which indicates DDIT4 plays a role in AILI. Ddit4

conclusionsIn summary, this study indicates the potential role of stem cell therapy in modulating mitochondrial function and highlights the role of activation the DDIT4/PGC-1α pathway in protecting hepatic mitochondria to alleviate AILI. This study provides a new mechanistic perspective for stem cell therapy in the treatment of AILI and potential targets for clinical drug development.

Indexed as

AcetaminophenChemical and Drug Induced Liver InjuryMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMitochondriaPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaTranscription FactorsAdipose TissueAnimalsDisease Models, AnimalHumansLiverMaleMiceMice, Inbred C57BLMice, KnockoutAcetaminophenDdit4 protein, mousePeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseTranscription FactorsAcetaminophenAcute liver failureDDIT4Mesenchymal stem cellsMitochondria

Identifiers

PMID41276869
PMCPMC12751710

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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.