Manganese superoxide dismutase gene therapy protects against irradiation- induced intestinal injury

Abstract

Radiation-induced intestinal injury is a common complication in radiotherapy for solid organ malignancies in abdomen or pelvis. However, currently there are no approved medical countermeasures for radiation-induced intestinal injury. Therefore, it is urgent to develop new treatments for radiation-induced intestinal injury. In the present study, we demonstrated that bone marrow derived mesenchymal stem cells (MSCs) and overexpression of human manganese superoxide dismutase (MnSOD) could ameliorate radiation-induced intestinal syndrome. NOD/SCID mice received abdominal irradiation at a selected dose of 5 Gy, and then infused intravenously with MnSOD-MSCs. Mice body weight, survival and diarrhea were monitored for 30-days. Colonization and differentiation of MnSOD-MSCs in the irradiated intestine were analyzed by histological and immunohistochemical methods. Consequently, our data demonstrated that intravenous administration of MnSOD-MSCs improved survival, decreased diarrhea occurrence and protected the small intestinal structural integrity of irradiated mice. Moreover, intravenously transplanted MnSOD-MSCs could colonize the irradiated intestine and repair injured sites. These findings suggested that MnSOD-MSCs may be an attractive and potential option for radiation-induced intestinal injury.