Therapeutic potentials of mesenchymal stem cells and their extracellular vesicles on liver diseases by modulating mitochondrial function of macrophages.

Macrophages play crucial roles in the progression of liver diseases. Increasing studies have shown that mesenchymal stem cells (MSCs) and their extracellular vesicles (MSC-EVs) could reshape the liver immune microenvironment by regulating the function and phenotype of macrophages, thereby exerting a therapeutic effect on liver diseases. Mitochondria, apart from being the central hub of energy metabolism, also finely regulate macrophage-mediated innate immune responses by modulating reactive oxygen species levels, cell polarization, and cell death. Mitochondrial dysfunction-associated abnormal macrophage function and phenotype is attracting increasing attention. In this review, we summarize the multiple types of mitochondrial damage in macrophages across various liver diseases and comprehensively discuss how MSCs can modulate macrophage mitochondrial function, including mitochondrial biogenesis and dynamics, mitophagy, and metabolic remodeling, or directly donate healthy mitochondria to alleviate liver diseases. A complete understanding of MSCs and MSC-EVs in the context of restoring mitochondrial function in macrophages may provide new insights for developing novel interventions targeting the immune microenvironment and innovative immunotherapeutic strategies for liver diseases.