Human mesenchymal stem cells promote survival and prevent intestinal damage in a mouse model of radiation injury

Abstract

Radiation-induced intestinal injury is a complex disease for which there is no effective treatment. Apoptosis of intestinal stem cells (ISCs) is the major cause of tissue damage, and replacing those ISCs with an alternative source of stem cells is gaining increasing interest as a potential therapeutic strategy for this condition. In the present study, we examined the protective effects of human umbilical cord mesenchymal stem cells (hMSCs) against ISC death and intestinal damage in a mouse model of radiation injury. hMSCs were introduced via tail vein injection in male C57BL/6J mice two hours after abdominal irradiation (AIR), and survival rates and weight changes were monitored over time. Cellular apoptosis in intestinal tissue was evaluated 6 h after AIR. Histological changes and survival of Lgr5⁺ ISCs were evaluated at days 3.5 and 5 post-AIR. Intestinal crypts were cultured ex vivo to further characterize the protective effects of hMSCs on ISCs. Ki67⁺ cells, vill⁺ enterocytes, lysozymes, CD31 vascular endothelial cells and α-smooth muscle actin were also examined by immunohistochemistry. Compared to mice treated with PBS after AIR, hMSC-treated mice exhibited improved survival, diminished weight loss, reduced radiation-induced apoptosis, attenuated structural damage of the small intestine, enhanced Lgr5⁺ ISC and Paneth cell survival, as well as increased Ki67⁺ transient amplifying cells and vill⁺ enterocytes. The distribution of CD31 vascular endothelial cells and α-smooth muscle actin demonstrated no significant difference between treatment groups. Our results demonstrate that hMSCs promote survival and attenuate intestinal damage by protecting Lgr5⁺ ISCs in a mouse model of radiation-induced injury.