Wahyu Widowati
1* 
, Adilah Hafizha Nur Sabrina
2, Annisa Firdaus Sutendi
2, Fadhilah Haifa Zahiroh
2, Teresa Liliana Wargasetia
1, Ita Margaretha Nainggolan
3,4, Elham Rismani
5* , Massoud Vosough
6,7,8* 1 Faculty of Medicine, Maranatha Christian University, Bandung 40164, Indonesia
2 Aretha Medika Utama, Biomolecular and Biomedical Research Center, Bandung 40163, Indonesia
3 Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Bogor, Indonesia
4 School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
5 Molecular Medicine Department, Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran
6 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran, Iran
7 Experimental Cancer Medicine, Institution for Laboratory Medicine, and Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
8 Department of Cellular and Molecular Biology, Faculty of Sciences and Advanced Technology in Biology, University of Science and Culture, Tehran, Iran
Abstract
Liver fibrosis (LF) is a pathological condition resulting from a chronic inflammatory response to multiple etiological factors, including viral infections, excessive alcohol consumption, and metabolic disorders. The important role of macrophages in this process, especially the M2 subtype, has attracted attention as a potential target for macrophage-based immunotherapy. M2 macrophages have anti-inflammatory and reparative properties that enable them to modulate the immune response and facilitate repairing damaged tissues. They participate in reducing fibrogenic features in term of gene expression and histological markers associated with LF. These cells phagocytose apoptotic cells and matrix components. M2 macrophage-based immunotherapy has shown great potential in ameliorating LF through mechanisms involving the IL-10/STAT3 and TGF-β/SMAD signaling pathways, which are essential in suppressing the pro-inflammatory response and supporting tissue regeneration. However, significant challenges such as individual resistance to therapy and the potential for promoting fibrosis suggest that further development and research are needed to optimize the safety and efficacy of this therapy in clinical applications. This study provides comprehensive insights into the role of M2 macrophages in LF and explores their potential as an innovative therapeutic approach in treating LF.