The Rehabilitation Influence Of Human Bone Marrow Mesenchymal Stem Cells On Radioactive Artery Injury

Clinical observations and experimental studies have proved that artery would be injured inevitably when treatment with radiation therapy on chest cancer. The arterial injuries mainly show as intimal thickening, thrombus formation, atherosclerosis, stenosis or occlusion. So far, corticosteroids, antibiotics and anticoagulant drugs was used to treat the side effects caused by radiotherapy. However, those treatments can only alleviate the symptoms and have no preventive effect on artery injury. Bone marrow mesenchymal stem cells (hBMSCs) are the important seed cells in regenerative medicine due to its powerful capacities of cytokines secretion, immune regulation, and multiple differentiation potential. HBMSCs also be reported to repair the vascular damage. Based on this, the present study was to investigate the effect and mechanisms of hBMSCs on radiation-induced artery injury. Samples of human bone marrow were collected from healthy volunteers and hBMSCs were isolated and cultured. 9 week old male C57/BL mice were used to build radioactive artery damage by the following protocol: mice were anesthesia and irradiated by 6MV-Xray of 18Gy once under the lungs shielded with lead sheaths. Then mice were randomly divided into four groups(n=25): the control group, the radiation group (18Gy-X ray +PBS), LD hBMSCs (18Gy-X ray +1× 103hBMSCs /g) and HD hBMSCs (18Gy-X ray +1× 104hBMSCs /g). The mice were received PBS or hBMSCs by tail vein injection after 24h of irradiation. After hBMSCs were injected 3 days, 7 days, 14 days, 28 days and 84 days, 5 of mice in each group were sacrificed and the aorta specimens were collected. It were observed that the vascular thickness, vascular cells apoptosis, vascular fibrosis, and the expression of inflammatory factors, fibrosis factors, and oxidative stress in the aorta by immunohistochemical staining and special staining. Radioactive artery damage model was successfully established, and by which, it was found that radiation induced artery injury, including the apoptosis of vascular cells, accumulation of collagen and thickening of artery wall. However, injection of hBMSCs in low or high dose could alleviate those pathological change of aorta. Radiation induced the expression of inflammatory factors (ICAM-1 and TNF-α), fibrosis factors (TGF-β1and CTGF) and oxidative damage (4-HNE and 3-NT) in aorta, while low or high dose of hBMSCs could inhibit the expression of those factors. Meanwhile, the high dose of hBMSCs had the more stronger effect than low dose of hBMSCs. Radiation induced the aortic injury, manifested in the increase of vascular cells apoptosis, the accumulation of collagen and thickening of aorta wall. HBMSCs could alleviate those aorta injuries induced by radiation possible by reduce the radiation induced inflammation, oxidative damage and fibrosis.