Exosomes Derived From Adipose-Derived Mesenchymal Stem Cells Ameliorate Radiation-Induced Brain Injury by Activating the SIRT1 Pathway

Frontiers in Cell and Developmental Biology

Dahai Hu²  Xuekang Yang²  Juntao Han²  Mengdong Liu²  Bin Zhao²  Jing Wang²  Kuo Shen²  Yunshu Yang²  Yuefan Yang³  Guoxu Zheng⁴ 

[1] Department of Biomedical Engineering, Air Force Military Medical University, Xi’an, China;Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, China;Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University, Xi’an, China;State key laboratory of Cancer Biology, Department of Immunology, Air Force Military Medical University, Xi’an, China;

关键词: radiation;    brain injury;    exosomes;    mesenchymal stem cells;    oxidative stress;   

DOI  :  10.3389/fcell.2021.693782

来源: DOAJ

【 摘 要 】

ObjectiveStudies have shown that the therapeutic effects of mesenchymal stem cells (MSCs) are mediated in a paracrine manner, mainly through extracellular vesicles such as exosomes. Here, we designed a study to investigate whether exosomes derived from adipose-derived mesenchymal stem cells (ADMSC-Exos) had protective effects in a rat model of radiation-induced brain injury and in microglia.MethodsMale adult Sprague-Dawley (SD) rats were randomly divided into three groups: the control group, the radiation group (30 Gy), and the radiation + exosomes group (30 Gy + 100 ug exosomes). Meanwhile, microglia were divided into four groups: the control group, the radiation group (10 Gy), the radiation + exosomes group (10 Gy + 4 ug exosomes), and radiation + exosomes + EX527 group (10 Gy + 4 ug exosomes + 100 nM EX527). Tissue samples and the levels of oxidative stress and inflammatory factors in each group were compared.ResultsStatistical analysis showed that after irradiation, ADMSC-Exos intervention in vivo significantly reduced the levels of caspase-3, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and promoted the recovery of superoxide dismutase (SOD), catalase (CAT), IL-4, and IL-10. Moreover, ADMSC-Exos intervention inhibited microglial infiltration and promoted the expression of SIRT1. Furthermore, the results in vitro showed that the above effects of ADMSC-Exos could be reversed by SIRT-1 inhibitor EX527.ConclusionThis study demonstrated that ADMSC-Exos exerted protective effects against radiation-induced brain injury by reducing oxidative stress, inflammation and microglial infiltration via activating the SIRT1 pathway. ADMSC-Exos may serve as a promising therapeutic tool for radiation-induced brain injury.

【 授权许可】

Unknown