Stromal vascular fraction for the treatment of the radiation-induced gastrointestinal syndrome

Abstract

Background & Aim Accidental or intended high doses radiation exposures have serious consequences for the health of exposed people and may impact a large number of people (as well as military than civil). Exposure of a large volume at high irradiation doses induces multiple tissue lesions grouped under the name of Acute Radiation Syndrome (ARS). The gastro-intestinal tract is especially sensitive to irradiation. At dose more than 10 Gy results in diarrhea, dehydration, sepsis and intestinal bleeding with death within 10 to 15 days post-exposure. Radiation-induced gastrointestinal syndrome results from direct cytocidal effects on intestinal stem cells and crypt stromal impairing epithelial regeneration. Irradiation rapidly reduces the mucosal integrity and promotes systemic bacteria influx resulting in sepsis and death. In this context, there is an urgent need for effective, rapid and applicable therapeutic measures for a large number of victims. Adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. We examined whether ADSVF protect irradiated intestinal cells niche and mitigate gastrointestinal syndrome. Methods, Results & Conclusion At the day of the abdominal irradiation (18Gy) mice were injected in systemic by the stromal vascular fraction (ADSVF) (2.5 106 cells), obtained through enzymatic digestion of inguinal adipose tissue. We found that, at 7 days post-irradiation, treatment with ADSVF limited the weight loss of mice and reduced the intestinal permeability. Immunohistological analyses in intestinal tissues revealed an increase of regenerating crypts, a restoration of the stromal compartment and an increase of Ki67+ proliferating cells in response to ADSVF treatment. In addition, the treatment reduced significantly the expression of cytokines associated to inflammatory response in intestine and normalized the splenic immune cells (CD4, CD8, CD19) populations and increased the C11b/Ly6Clow/Cx3cr1 population. Treatment in emergency of gastrointestinlal syndrome could be achieved by intravenous injection of ADSVF inducing regeneration of intestine.