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

Abstract

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 na.ve endothelial cells with detected by IHC-staining, and the vascular integrity was evaluated by measuring VE-Cadherin. The origination of na.ve 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. Key words: Adipose-derived mesenchymal stem cells; Radiation-induced intestinal injury; Blood vessel; Repairation