Gastric cancer (GC) is one of the most prevalent malignancies in the world, with a high mortality rate in both women and men. Conventional treatments, like chemotherapy, radiotherapy and surgery, are facing some drawbacks like acquired drug resistance and various side effects, leading to cancer recurrence and increased morbidity; thus, development of novel approaches in targeted therapy would be very beneficial. Exosomes, extracellular vesicles with a size distribution of sub-150 nm, interplay in physiological and pathophysiological cell–cell communications and can pave the way for targeted cancer therapy. Accumulating pieces of evidence have indicated that exosomes derived from mesenchymal stem cells (MSC-EXs) can act as a double-edged sword in some cancers. The purpose of this review is to assess the differences between stem cell therapy and exosome therapy. Moreover, our aim is to demonstrate how naïve MSCs transform into GC-MSCs in the tumor microenvironment. Additionally, the tumorigenic and anti-proliferation effects of MSC-EXs derived from different origins were investigated. Finally, we suggest potential modifications and combination options that involve utilizing MSC-EXs from the foreskin and umbilical cord as promising sources to enhance the efficacy of gastric cancer treatment. This approach is presented in contrast to bone marrow cells, which are more heterogeneous, age-related, and are also easily affected by the patient\\\\\\\'s circulation system.

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