Abstract
The present study aims to explore the protective effect of human bone marrow mesenchymal stem cells (hBMSCs) on radiation-induced aortic injury (RIAI). hBMSCs were isolated and cultured from human bone marrow. Male C57/BL mice were irradiated with a dose of 18-Gy 6MV X-ray and randomly treated with either vehicle or hBMSCs through tail vein injection with a dose of 103 or 104 cells/g of body weight (low or high dose of hBMSCs) within 24 h. Aortic inflammation, oxidative stress, and vascular remodeling were assessed by immunohistochemical staining at 3, 7, 14, 28, and 84 days after irradiation. The results revealed irradiation caused aortic cell apoptosis and fibrotic remodeling indicated by aortic thickening, collagen accumulation, and increased expression of profibrotic cytokines (CTGF and TGF-β). Further investigation showed that irradiation resulted in elevated expression of inflammation-related molecules (TNF-α and ICAM-1) and oxidative stress indicators (4-HNE and 3-NT). Both of the low and high doses of hBMSCs alleviated the above irradiation-induced pathological changes and elevated the antioxidant enzyme expression of HO-1 and catalase in the aorta. The high dose even showed a better protective effect. In conclusion, hBMSCs provide significant protection against RIAI possibly through inhibition of aortic oxidative stress and inflammation. Therefore, hBMSCs can be used as a potential therapy to treat RIAI.
Highlights
Radiotherapy is an important treatment for malignant tumors
Morphology and Features of human bone marrow mesenchymal stem cells (hBMSCs). 2 weeks after isolation and culture by density gradient centrifugation combined with individual colonies screening, P1 hBMSCs reached 80% confluence and were passaged every 4-5 days for 9–12th passages without morphologic alteration. hBMSCs displayed fibroblast-like shape and homogenous and vortex-like growth in monolayers (Figure 1(a))
These results indicated that the cultured cells with relative homogeneity exhibited the characteristics of hBMSCs
Summary
Normal tissues surrounding the tumor would be irradiated and damaged. When thoracic malignancies undergo radiotherapy, the thoracic aorta and other surrounding blood vessels are inevitably subject to radiation damage. Radiation-induced arterial injury (RIAI) was first reported in 1959 and considered as a chronic damage due to its insidious development for decades before the appearance of clinical symptoms [1]. The main clinical manifestations of RIAI are atherosclerosis, stenosis, and obstruction [1]. It could occur in a variety of locations, including carotid artery [3], arteries of the upper limbs, axillary artery [4], and subclavian artery [5]. High-dose radiotherapy is a significant risk factor of accelerated carotid atherosclerotic disease [7]
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