title: Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells.
abstract: Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow-derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague-Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury.
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Yi-Xing
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China zeng.zhaochong@zs-hospital.sh.cn.
authors.forename: Zhao-Chong
authors.initials: ZC
authors.lastname: Zeng
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zeng
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Yan-
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018836:Inflammation Mediators
keywords: apoptosis; mesenchymal stem cell; radiation-induced liver injury; sinusoidal endothelial cell