Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation

Abstract Background Apical papilla stem cells (SCAPs) exhibit significant potential for tissue repair, characterized by their anti-inflammatory and pro-angiogenic properties. Exosomes derived from stem cells have emerged as safer alternatives that retain comparable physiological functions. This stud...

Full description

Saved in:
Bibliographic Details
Main Authors: Yifei Nie, Wenqing Meng, Duanqin Liu, Ziqing Yang, Wenhao Wang, Huiping Ren, Kai Mao, Weipeng Lan, Chuanhua Li, Zhifeng Wang, Jing Lan
Format: Article
Language:English
Published: BMC 2024-10-01
Series:Molecular Medicine
Subjects:
Online Access:https://doi.org/10.1186/s10020-024-00945-1
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850203554003812352
author Yifei Nie
Wenqing Meng
Duanqin Liu
Ziqing Yang
Wenhao Wang
Huiping Ren
Kai Mao
Weipeng Lan
Chuanhua Li
Zhifeng Wang
Jing Lan
author_facet Yifei Nie
Wenqing Meng
Duanqin Liu
Ziqing Yang
Wenhao Wang
Huiping Ren
Kai Mao
Weipeng Lan
Chuanhua Li
Zhifeng Wang
Jing Lan
author_sort Yifei Nie
collection DOAJ
description Abstract Background Apical papilla stem cells (SCAPs) exhibit significant potential for tissue repair, characterized by their anti-inflammatory and pro-angiogenic properties. Exosomes derived from stem cells have emerged as safer alternatives that retain comparable physiological functions. This study explores the therapeutic potential of exosomes sourced from SCAPs in the treatment of non-alcoholic steatohepatitis (NASH). Methods A NASH mouse model was established through the administration of a high-fat diet (HFD), and SCAPs were subsequently isolated for experimental purposes. A cell model of NASH was established in vitro by treating hepatocellular carcinoma cells with oleic acid (OA) and palmitic acid (PA). Exosomes were isolated via differential centrifugation. The mice were treated with exosomes injected into the tail vein, and the hepatocytes were incubated with exosomes in vitro. After the experiment, physiological and biochemical markers were analyzed to assess the effects of exosomes derived from SCAPs on the progression of NASH in both NASH mouse models and NASH cell models. Results After exosomes treatment, the weight gain and liver damage induced by HFD were significantly reduced. Additionally, hepatic fat accumulation was markedly alleviated. Mechanistically, exosomes treatment promoted the expression of genes involved in hepatic fatty acid oxidation and transport, while simultaneously suppressing genes associated with fatty acid synthesis. Furthermore, the levels of serum inflammatory cytokines and the mRNA expression of inflammatory markers in liver tissue were significantly decreased. In vitro cell experiments produced similar results.
format Article
id doaj-art-5e45fa33d8df4cb8b445c5e12cd0fae9
institution OA Journals
issn 1528-3658
language English
publishDate 2024-10-01
publisher BMC
record_format Article
series Molecular Medicine
spelling doaj-art-5e45fa33d8df4cb8b445c5e12cd0fae92025-08-20T02:11:29ZengBMCMolecular Medicine1528-36582024-10-0130111610.1186/s10020-024-00945-1Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammationYifei Nie0Wenqing Meng1Duanqin Liu2Ziqing Yang3Wenhao Wang4Huiping Ren5Kai Mao6Weipeng Lan7Chuanhua Li8Zhifeng Wang9Jing Lan10Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesAbstract Background Apical papilla stem cells (SCAPs) exhibit significant potential for tissue repair, characterized by their anti-inflammatory and pro-angiogenic properties. Exosomes derived from stem cells have emerged as safer alternatives that retain comparable physiological functions. This study explores the therapeutic potential of exosomes sourced from SCAPs in the treatment of non-alcoholic steatohepatitis (NASH). Methods A NASH mouse model was established through the administration of a high-fat diet (HFD), and SCAPs were subsequently isolated for experimental purposes. A cell model of NASH was established in vitro by treating hepatocellular carcinoma cells with oleic acid (OA) and palmitic acid (PA). Exosomes were isolated via differential centrifugation. The mice were treated with exosomes injected into the tail vein, and the hepatocytes were incubated with exosomes in vitro. After the experiment, physiological and biochemical markers were analyzed to assess the effects of exosomes derived from SCAPs on the progression of NASH in both NASH mouse models and NASH cell models. Results After exosomes treatment, the weight gain and liver damage induced by HFD were significantly reduced. Additionally, hepatic fat accumulation was markedly alleviated. Mechanistically, exosomes treatment promoted the expression of genes involved in hepatic fatty acid oxidation and transport, while simultaneously suppressing genes associated with fatty acid synthesis. Furthermore, the levels of serum inflammatory cytokines and the mRNA expression of inflammatory markers in liver tissue were significantly decreased. In vitro cell experiments produced similar results.https://doi.org/10.1186/s10020-024-00945-1Apical papilla stem cell-derived exosomesNASHAMPKPPARα
spellingShingle Yifei Nie
Wenqing Meng
Duanqin Liu
Ziqing Yang
Wenhao Wang
Huiping Ren
Kai Mao
Weipeng Lan
Chuanhua Li
Zhifeng Wang
Jing Lan
Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
Molecular Medicine
Apical papilla stem cell-derived exosomes
NASH
AMPK
PPARα
title Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
title_full Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
title_fullStr Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
title_full_unstemmed Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
title_short Exosomes derived from apical papilla stem cells improve NASH by regulating fatty acid metabolism and reducing inflammation
title_sort exosomes derived from apical papilla stem cells improve nash by regulating fatty acid metabolism and reducing inflammation
topic Apical papilla stem cell-derived exosomes
NASH
AMPK
PPARα
url https://doi.org/10.1186/s10020-024-00945-1
work_keys_str_mv AT yifeinie exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT wenqingmeng exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT duanqinliu exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT ziqingyang exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT wenhaowang exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT huipingren exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT kaimao exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT weipenglan exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT chuanhuali exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT zhifengwang exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation
AT jinglan exosomesderivedfromapicalpapillastemcellsimprovenashbyregulatingfattyacidmetabolismandreducinginflammation