Exosomes and Autophagy: A New Frontier in Cell Communication and Regeneration

Exosomes are nanoscale vesicles derived from the cell membrane that are released by various cell types. They play important roles in cell communication, cancer metastasis, immune modulation, and infectious agent transmission [201]. Studies have shown that exosome biogenesis and macroautophagy share molecular machinery and regulatory mechanisms, indicating a close relationship between the two processes [202].

While many studies have focused on the positive effects of exosomes on other stem cells, few have explored the regulation of autophagy by exosomes and their contained miRNAs. Most studies on exosomes and autophagy have centered on liver injury and regeneration. For instance, BMMSC-derived hepatocyte-like cell-derived exosomes (MSC-Heps-Exos) have been shown to effectively inhibit hepatocyte apoptosis, relieve hepatic I/R damage, and decrease liver enzyme levels through autophagy activation [205]. In ALD and AH mouse models, as well as in human livers with ALD, autophagic flux was seriously impaired by miRNA-155 increase [206]. However, recent reviews have highlighted the potential of MSC-derived exosomes to activate autophagy and inhibit apoptosis or necrosis in other injured cells, such as retinal cells, neurons, epithelial cells in lung, gut, and renal, promoting their survival and regeneration [207].

Exosomes and their miRNA cargos hold promise as biomolecular manipulation approaches to regulate autophagy equilibrium. While exosomes have been shown to be useful in oral tissue regeneration, the special link between autophagy and exosomes remains poorly understood. Therefore, further research should focus on the relationship among exosomes, miRNAs, and autophagy [208, 209].