Adipose-derived mesenchymal stem cell therapy for radiation-induced vascular injury in small intestine of rat

Objective: To assess the therapeutic effect of human adipose-derived mesenchymal stem cells on radiation-induced vascular injury in the small intestine of rat. Methods: A total of 34 male Sprague-Dawley rats were enrolled in this study. To establish a model of radiation-induced intestinal injury, each rat was irradiated with 15 Gy in whole abdomen. 17 rats were randomly selected and infused intraperitoneally with passage 6 (P6) Ad-MSCs, and the other 17 rats that received PBS were set as control. 10 days post-irradiation, the number of CD31+ endothelial cells in the small intestine villus was measured by flow-cytometry, the expressions of CD31, CD105 and isolectin-B4 in the naïve endothelial cells with detected by IHC-staining, and the vascular integrity was evaluated by measuring VE-Cadherin. The origination of naïve endothelial cells within injured intestine was also analyzed. In addition, total mRNA were extracted from irradiated small intestine to assay the expressions of VEGF, bFGF, Flk-1 and SDF-1 using quantitative Real-time PCR. Results: Compared to the control, the amount of CD31-postive endothelial cells within irradiated intestine was significantly increased after Ad-MSCs infusion (t = 12.15, P < 0.05). The microvascular density in the injured sites was also significantly increased by the infusion of Ad-MSCs (20 d: t = 10.33, P < 0.05; 30 d: t = 32.85, P < 0.05). Moreover, the expressions of VEGF, bFGF, Flk-1 and SDF-1 were significantly up-regulated after delivery of Ad-MSCs (VEGF:t = 10.34, bFGF:t = 11.25, Flk-1:t = 6.73, SDF-1:t = 6.73, all P < 0.05), which was beneficial in maintaining the integrity of intra-villus blood-vessels as well as promoting neovascularization in the injured sites. Conclusion: Ad-MSCs had potentials in healing radiation-induced vascular injury in rat small intestine. (authors)