Discov Oncol. 2026 Jan 03.
BACKGROUND: Mesenchymal stem cell (MSC)-derived exosomes revealed therapeutic ability, particularly in cancer treatment, by transferring bioactive molecules like miRNAs. Hypoxia, a common tumor condition, influences both tumor progression and MSC behavior. This review explores how hypoxic conditions affect MSC-derived exosomes and their impact on cancer-related pathways and genes.
METHOD: The current systematic review study was conducted by searching four different databases, including PubMed, Scopus, Embase, and Web of Science, using keywords such as mesenchymal stem cells, exosomes, hypoxia, cancer, and related terms. All original pre-clinical studies that focused on the role and effect of hypoxia in MSC-derived extracellular vesicles in different cancers were included. Data were collected qualitatively.
RESULT: Overall, 264 articles were identified from searching in databases, and eight of them met the eligibility criteria and were included in the current study. Among the articles, four focused on lung cancer, two on breast cancer, one on hepatocellular carcinoma, and one on Multiple Myeloma. The results indicated that MSC-derived exosomes have an enhanced effect on cell viability, migration, proliferation, and invasion of cancerous cells both in vitro and in vivo settings, and also cause a reduction in apoptosis in these cells. Besides, hypo MSC-exosomes can change the expression of some miRNAs in cancer cells, which affect different signaling pathways.
CONCLUSION: In general, the current study suggests that hypoxia-preconditioning of MSC-derived exosomes can influence specific genes, miRNAs, and signaling pathways in cancer cells, leading to increased proliferation, migration, and invasion, as well as decreased apoptosis. Besides, the biological effects of hypoxia-modulated exosomes seem to be significantly context-dependent. Although they may exacerbate malignancy in cancer microenvironments, analogous pathways can also facilitate tissue repair and regeneration in non-cancerous situations.
Keywords: Cancer; Exosomes; Extracellular vesicles; Hypoxia; MSC; Malignancy; Mesenchymal stem cells; Neoplasms