Mesenchymal stem cell implantation mitigates ionizing radiation-induced vascular damage in the murine aorta

For preparedness for some scenarios such as unintentional accidents or intentional malicious events, it is of critical importance to develop effective medical countermeasures against normal tissue injury from exposure to ionizing radiation. To this end, agents that are effective when administered after radiation exposure need to be developed. Considering that vascular injury is among the upstream events of radiation toxicity in various tissues, the present study was undertaken to investigate whether post-irradiation implantation of human mesenchymal stem/stromal cells (MSCs) restore vascular injury induced by acute irradiation. MSCs were obtained from human adipose tissue. For in vivo experiments, young adult male C57BL/6J mice (n = 8/group) were received intravenous injection of 5 × 10⁴ MSCs or vehicle at 6 h after irradiation with 5 Gy (sublethal dose) of ¹³⁷Cs γ-rays. Control mice were sham-irradiated and received vehicle injection. At four weeks after irradiation, the aorta was collected, and subjected to scanning electron microscopy, immunofluorescence and histochemistry staining. Irradiation led to various changes in the aorta of mice, such as detachment and partial loss of the endothelium, decreases in vascular endothelial cadherin and endothelial nitric oxide synthase, vascular endothelial and smooth muscle cell death, inflammation (evidenced by increases in CD68, F4/80 and CD3) and fibrosis (evidenced by increases in transforming growth factor β1 and collagen). Post-irradiation MSC implantation restored such radiation-induced vascular damage.