The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice
Résumé
Background: The intestine is particularly sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. There is an urgent need for effective and rapid therapeutic countermeasures. The stromal vascular fraction (SVF) derived from adipose tissue is an easily accessible source of cells with angiogenic, anti-inflammatory and regenerative properties. We studied the therapeutic impact of SVF and its action on the intestinal stem cell compartment. Methods: Mice exposed to the abdomina l radiation (18 Gy) received a sing l e intravenous injection of stroma l vascu l ar fraction (SVF) (2.5 x 106 ce l l s), obtained by enzymatic digestion of inguina l fat tissue, on the day of irradiation. Morta l ity was eva l uated as we l l as intestina l regeneration by histologica l ana l yses and absorption function. Results: The SVF treatment l imited the weight l oss of the mice and inhibited the intestina l permeabi l ity and morta l ity after abdomina l irradiation. Histo l ogica l ana l yses showed that SVF treatment stimu l ated the regeneration of the epithe l ium by promoting numerous en l arged hyperpro l iferative zones. SVF restored CD24+/lysozyme_ and Paneth ce l l popu l ations in the ISC compartment with the presence of Paneth Ki67+ ce l l s. SVF has an anti-infl ammatory effect by repressing proinfl ammatory cytokines, increasing M2 macrophages in the il eum and anti-infl ammatory monocyte subtypes CD11 b+Ly6clowCX3CR1hgh in the spl een. Conclusions: Through the p l eiotropic effects that contribute to l imiting radiation-induced l etha l ity, SVF opens up attractive prospects for the treatment of emergency GIS.
Domaines
ToxicologieOrigine | Publication financée par une institution |
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