Fig. 2
MSC-derived EVs extend the life and reduced intestinal permeability of NUDE mice subjected to 10 Gy WBI. a–c Nude mice received 10 Gy WBI (a) black arrow. Mice were randomly assigned to three different groups. Control mice received the vehicle (first group). MSC were intravenously administered in a single injection of 5 million cells, 6 h after WBI (second group (a), only the first gray arrow). A total of 600 μg of MSC-derived EVs was intravenously administered in three 200-μg injections 6 h, 24 h, and 48 h after WBI (third group (a), the three gray arrows). a The survival rate of mice was evaluated. Each value results from one representative experiment (N = 1, 19 mice in the 10-Gy WBI group treated with PBS, 11 mice in the 10-Gy WBI group treated with MSC, and 11 mice in the 10-Gy WBI group treated with MSC-derived EVs). The mouse survival curves were calculated using the Kaplan-Meier method, and the p value was determined by the log-rank test eventually adjusted for multiple comparisons. $$$p ≤ 0.0001 compared with the 10-Gy WBI group. The survival Cox model was used in the assessment of the association between MSC-derived EV treatment and the instantaneous risk of death. b Three days after WBI, all mice were orally gavaged with 75 mg/ml of 4 kDa FITC-labeled dextran, and 5 h later, blood samples were collected. The small intestinal permeability was determined by a plasmatic dosage of 4 kDa FITC-labeled dextran (mg/ml). Each value represents the average values coming from 3 independently repeated experiments (N = 3, 2 to 12 animals per group and experiment), ***p ≤ 0.0001 compared with the non-irradiated group, $$p ≤ 0.001 compared with the 10-Gy WBI group. c Representative pictures of claudin-3 immunostaining in the small intestine of non-irradiated NUDE mice (1 and 5), 3 days after 10 Gy WBI (2 and 6), 3 days after 10 Gy WBI and treatment with 5.106 hMSC (3 and 7), and 3 days after 10 Gy WBI and treatment with MSC-derived EVs. Scale bar 100 μm for (1–4) and 50 μm for (5–8)