Abstract: BACKGROUND: The biological functions and characteristics of pretreated exosomes have been extensively studied and verified in the treatment of some diseases and achieved good results, suggesting that they may also have broader prospects in the field of tissue regeneration and clinical applications.
OBJECTIVE: To mainly explore the pretreatment methods of donor cells of pretreated exosomes and the influence of pretreatment factors on the function of exosomes and to summarize the effects and current status of clinical application of different pretreated exosomes on cell proliferation, differentiation, and apoptosis.
METHODS: PubMed, Web of Science, CNKI, and WanFang databases were searched for relevant articles. The retrieval terms were “exosomes, small extracellular vesicles, pretreatment” in Chinese and “pretreatment, cell factor, hypoxia, ischemia” in English. A total of 75 articles were finally included in result analysis. 
RESULTS AND CONCLUSION: (1) Although the cell-derived exosomes have good biocompatibility and low immunogenicity, they have some shortcomings, such as low yield and weak targeting. Their biological properties highly depend on the state, type, and culture environment of cells. Pretreatment of cells and their microenvironment can affect the contents and level of the obtained exosomes. (2) Common exosome pretreatment methods include cytokines, anoxia/hypoxia, drugs and physical intervention. The exosomes obtained by different cells or different pretreatment methods may have different biological characteristics. (3) Compared with the untreated exosomes, the pretreated exosomes can regulate cell proliferation and apoptosis, osteogenic differentiation, and angiogenesis. Their functional properties have obvious advantages and play a biological role efficiently. (4) The pretreated exosomes play an important role in tissue repair and disease treatment, which have been successfully used in the treatment of ischemic diseases, immune function regulation, and inflammatory diseases. (5) Pretreatment, as an effective stimulus for cell “modification,” has shown outstanding advantages in the field of exosome research. It can not only be applied to disease treatment and regulation, but also has a good application prospect in tissue engineering regeneration and repair. As an adaptive strategy to improve exosome production and biological effects, its specific mechanism and functional conditions need to be further studied.

Key words: exosome, pretreatment, cell, proliferation, migration, differentiation, apoptosis, application