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Radiation therapy for cancers also damages healthy cells and causes side effects. Depending on the dosage and exposure region, radiotherapy may induce severe and irreversible injuries to various tissues or organs, especially the skin, intestine, brain, lung, liver, and heart. Therefore, promising treatment strategies to mitigate radiation injury is in pressing need. Recently, stem cell-based therapy generates great attention in clinical care. Among these, mesenchymal stem cells are extensively applied because it is easy to access and capable of mesodermal differentiation, immunomodulation, and paracrine secretion. Here, we summarize the current attempts and discuss the future perspectives about mesenchymal stem cells (MSCs) for mitigating radiotherapy side effects. [ABSTRACT FROM AUTHOR]