A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update

Abstract Hepatocellular carcinoma (HCC) is a significant global health challenge, being one of the leading causes of cancer-related mortality. This review focuses on the intricate interactions within the tumor microenvironment and mesenchymal stem cells (MSCs) and it’s secretome in HCC and possible...

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Main Authors: Jayenth Jayachandran, A. T. Rithi, Abhijit Mitra, Arunkumar Radhakrishnan, Antara Banerjee, Asim K. Duttaroy
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03088-9
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author Jayenth Jayachandran
A. T. Rithi
Abhijit Mitra
Arunkumar Radhakrishnan
Antara Banerjee
Asim K. Duttaroy
author_facet Jayenth Jayachandran
A. T. Rithi
Abhijit Mitra
Arunkumar Radhakrishnan
Antara Banerjee
Asim K. Duttaroy
author_sort Jayenth Jayachandran
collection DOAJ
description Abstract Hepatocellular carcinoma (HCC) is a significant global health challenge, being one of the leading causes of cancer-related mortality. This review focuses on the intricate interactions within the tumor microenvironment and mesenchymal stem cells (MSCs) and it’s secretome in HCC and possible therapeutic responses. MSCs, characterized by their multipotent differentiation and self-renewal capabilities, can influence tumor behavior maybe through its secreted factors, including cytokines, growth factors and extracellular vesicles. This review summarizes the recent findings on role of MSCs in HCC, highlighting its involvement in different cell signaling pathways, including NF-κB, Wnt/β-catenin, Notch1, Stat3, and TGF-β, which play a significant role in HCC and possibly exhibit both tumor-suppressive and/or tumor-promoting effects depending on the activation or deactivation of signaling pathways. Publications related to the topic between 2016 to 2025 were searched using databases like PubMed, Scopus, Google Scholar with keywords viz. HCC, mesenchymal stem cells, secretome, tumor microenvironment, and signaling pathways. Findings from different research studies depict that MSCs and their secretome can exert anti-tumor effects by inducing apoptosis and enhancing immune responses, they may also promote alternate effects like tumor proliferation and metastasis under certain conditions, related to the activation or deactivation of different signalling pathways. This review aims to provide a comprehensive understanding of the multifaceted roles of MSCs in HCC. The dual role and the complexities of MSCs is context dependent. However, advancements in MSC research showed that the modifications of MSCs and secretome-based therapies and targeting the signaling pathways may have the potential to overcome challenges like drug resistance in HCC treatment.
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spelling doaj-art-6ec0e8b51db04b3089b1e7e4fc964a182025-08-20T03:05:09ZengSpringerDiscover Oncology2730-60112025-07-0116111910.1007/s12672-025-03088-9A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent updateJayenth Jayachandran0A. T. Rithi1Abhijit Mitra2Arunkumar Radhakrishnan3Antara Banerjee4Asim K. Duttaroy5Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)Medical Biotechnology Lab, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)Medical Biotechnology Lab, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE)Department of Nutrition, Institute of Medical Sciences, Faculty of Medicine, University of OsloAbstract Hepatocellular carcinoma (HCC) is a significant global health challenge, being one of the leading causes of cancer-related mortality. This review focuses on the intricate interactions within the tumor microenvironment and mesenchymal stem cells (MSCs) and it’s secretome in HCC and possible therapeutic responses. MSCs, characterized by their multipotent differentiation and self-renewal capabilities, can influence tumor behavior maybe through its secreted factors, including cytokines, growth factors and extracellular vesicles. This review summarizes the recent findings on role of MSCs in HCC, highlighting its involvement in different cell signaling pathways, including NF-κB, Wnt/β-catenin, Notch1, Stat3, and TGF-β, which play a significant role in HCC and possibly exhibit both tumor-suppressive and/or tumor-promoting effects depending on the activation or deactivation of signaling pathways. Publications related to the topic between 2016 to 2025 were searched using databases like PubMed, Scopus, Google Scholar with keywords viz. HCC, mesenchymal stem cells, secretome, tumor microenvironment, and signaling pathways. Findings from different research studies depict that MSCs and their secretome can exert anti-tumor effects by inducing apoptosis and enhancing immune responses, they may also promote alternate effects like tumor proliferation and metastasis under certain conditions, related to the activation or deactivation of different signalling pathways. This review aims to provide a comprehensive understanding of the multifaceted roles of MSCs in HCC. The dual role and the complexities of MSCs is context dependent. However, advancements in MSC research showed that the modifications of MSCs and secretome-based therapies and targeting the signaling pathways may have the potential to overcome challenges like drug resistance in HCC treatment.https://doi.org/10.1007/s12672-025-03088-9Hepatocellular carcinomaMesenchymal stem cellsMSC secretomeTumor microenvironmentExtracellular vesiclesTherapeutic intervention
spellingShingle Jayenth Jayachandran
A. T. Rithi
Abhijit Mitra
Arunkumar Radhakrishnan
Antara Banerjee
Asim K. Duttaroy
A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update
Discover Oncology
Hepatocellular carcinoma
Mesenchymal stem cells
MSC secretome
Tumor microenvironment
Extracellular vesicles
Therapeutic intervention
title A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update
title_full A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update
title_fullStr A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update
title_full_unstemmed A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update
title_short A review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways: recent update
title_sort review on mesenchymal stem cells and their secretome in hepatocellular carcinogenesis and its related signaling pathways recent update
topic Hepatocellular carcinoma
Mesenchymal stem cells
MSC secretome
Tumor microenvironment
Extracellular vesicles
Therapeutic intervention
url https://doi.org/10.1007/s12672-025-03088-9
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