Immunomodulatory Effects of Stem Cell Therapy in Liver Fibrosis: A Systematic Review

Liver fibrosis is known as a condition characterized by chronic inflammation and excessive extracellular matrix deposition that causes cirrhosis and liver failure. Stem cell therapy is a promising strategy for the management of liver fibrosis because it not only improves tissue regeneration but also modulates by immunomodulatory mechanisms. This systematic review aimed to evaluate the immunoregulatory effects of stem cells in both experimental models and clinical studies of liver fibrosis. A total of 29 studies were included, comprising several stem cell sources, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (AT-MSCs), and stem cells from human exfoliated deciduous teeth (SHED), among others. Studies reported that stem cells could decrease proinflammatory cytokines (e.g., TNF-α, IFN-γ, IL-17) and fibrosis-related markers, while increasing levels of anti-inflammatory cytokines (e.g., IL-10, IL-4) and regulatory immune cells such as Tregs (regulatory T cells). Stem cells could affect immune homeostasis via modulating in macrophage polarization, T cell subsets, and B cell activity, resulting in attenuated fibrotic progression and improved liver function. Despite variability in cell types, routes of administration, and fibrosis models, the results support the potential of stem cell therapy to reform the hepatic immune microenvironment. However, more standardized protocols and clinical validations are required. This study emphasizes the immunomodulatory potential of stem cells as a therapeutic method in liver fibrosis. It brings a clear view into their mechanisms of action and the foundation for future translational applications.