**1. Introduction**

Malignant tumors are one of the most aggressive diseases and have high mortality. Currently, there are no efficient methods capable of eradicating cancers clinically. As a conventional cancer treatment modality, radiotherapy (RT) can kill cancer cells and improve patient survival rates. Unfortunately, cancer patients also have to risk radiotoxicity to healthy tissues around the tumor. Clinical studies have revealed skin, intestinal, brain, pulmonary, hepatic, and cardiovascular injuries in cancer patients who received RT [1–5]. Although developments in RT devices and techniques (e.g., intensity-modulated RT, IMRT; image-guided RT, IGRT.) have significantly decreased radiation dose, exposure volume, and area, radiation injury is still unavoidable [6–9]. There is no evidence showing the existing dose threshold that would not damage the cell [10]. Emerging epidemiological data have consistently confirmed that low-dose radiation could also cause tissue damage [11,12]. Thus, when optimizing the RT technique to reduce the risk of radiation exposure, more effort should be made to seek satisfactory treatment for radiation-induced tissue injury.

In recent decades, stem cells have become a hot topic of research in regenerative medicine, bioengineering, and other clinical settings. Among the various stem cell types, mesenchymal stem cells (MSCs) are the most frequently studied. Thousands of publications are issued, and more than 490 clinical trials utilizing MSCs have been carried out or ongoing [13]. The reasons might be that MSCs are easy to access due to their abundant resources, including bone marrow, adipose tissue, umbilical cord, and placental tissue. Additionally, MSCs possess stable genomes, great self-renewal ability, mesodermal differentiation capacity, and immunomodulatory and paracrine secretome [14]. Indeed, MSCs reveal the tremendous therapeutic potential in various diseases such as cancer, diabetes mellitus,

**Citation:** Wang, K.-X.; Cui, W.-W.; Yang, X.; Tao, A.-B.; Lan, T.; Li, T.-S.; Luo, L. Mesenchymal Stem Cells for Mitigating Radiotherapy Side Effects. *Cells* **2021**, *10*, 294. https://doi.org/ 10.3390/cells10020294

Academic Editors: Alexander Ljubimov and Alain Chapel Received: 24 November 2020 Accepted: 29 January 2021 Published: 1 February 2021

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autoimmune disease, liver injury, and cardiovascular disease [15–19]. Thus, scientists attempt to investigate whether MSCs therapy could also mitigate radiation injury. Here, we will first introduce the underlying mechanisms of radiation injury and the features of MSCs briefly. Then, we focus on the recent progress on MSCs therapy in treating radiation injury. Last, we discuss the challenges and future perspectives of the MSCs therapy.
