Manganese Superoxide Dismutase Gene-Modified Mesenchymal Stem Cells Attenuate Acute Radiation-Induced Lung Injury

被引：41

作者：

Chen, Hai-Xu ^{[1
]}

Xiang, Hang ^{[1
]}

Xu, Wen-Huan ^{[1
]}

Li, Ming ^{[2
]}

Yuan, Jie ^{[3
,4
]}

Liu, Juan ^{[3
,4
]}

Sun, Wan-Jun ^{[3
,4
]}

Zhang, Rong ^{[3
,4
]}

Li, Jun ^{[3
,4
]}

Ren, Zhao-Qi ^{[3
,4
]}

Zhang, Xiao-Mei ^{[1
]}

Du, Bin ^{[3
,4
]}

Wan, Jun ^{[1
]}

Wu, Ben-Yan ^{[1
]}

Zeng, Qiang ^{[1
]}

He, Kun-Lun ^{[1
]}

Yang, Chao ^{[1
,3
,4
]}

机构：

[1] Chinese Peoples Liberat Army, Lab Basic Res & Translat Med Chron Heart Failure, Core Lab Translat Med,Gastrointestinal Dept South, Inst Geriatr,Hlth Management Inst,Gen Hosp, Beijing, Peoples R China

[2] Soochow Univ, Coll Med, Sch Radiat Med & Protect, Suzhou, Peoples R China

[3] PLA Rocket Force, Gen Hosp, Dept Hematol, Beijing, Peoples R China

[4] PLA Rocket Force, Gen Hosp, Dept Blood Transfus, Xinjiekouwai St 16, Beijing 100088, Peoples R China

来源：

HUMAN GENE THERAPY | 2017年 / 28卷 / 06期

基金：

美国国家科学基金会;

关键词：

radiation-induced lung injury; mesenchymal stem cells; manganese superoxide dismutase; cell therapy; STROMAL CELLS; INFLAMMATION; PNEUMONITIS; MECHANISMS; PROTECTS; FIBROSIS; THERAPY; MNSOD; MODEL; RISK;

D O I：

10.1089/hum.2016.106

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Radiation-induced lung injury (RILI) is a major clinical complication for radiotherapy in thoracic tumors. An immediate effect of lung irradiation is the generation of reactive oxygen that can produce oxidative damage to DNA, lipids, and proteins resulting in lung cell injury or death. Currently, the medical management of RILI remains supportive. Therefore, there is an urgent need for the development of countermeasures. The present study aimed to evaluate the protective effect of manganese superoxide dismutase (MnSOD) gene-modified mesenchymal stem cells (MSCs) to facilitate the improved recovery of RILI. Here, nonobese diabetic/severe combined immunodeficiency mice received a 13Gy dose of whole-thorax irradiation, and were then transfused intravenously with MnSOD-MSCs and monitored for 30 days. Lung histopathologic analysis, plasma levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10, and tumor necrosis factor-alpha), profibrotic factor transforming growth factor-beta 1, and the oxidative stress factor (hydroxyproline) were evaluated after MnSOD-MSC transplant. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated nick-end labeling immunohistochemical method. Colonization and differentiation of MnSOD-MSCs in the irradiated lung were analyzed by immunofluorescence staining. Consequently, systemic administration of MnSOD-MSCs significantly attenuated lung inflammation, ameliorated lung damage, and protected the lung cells from apoptosis. MnSOD-MSCs could differentiate into epithelial-like cells in vivo. MnSOD-MSCs were effective in modulating RILI in mice and had great potential for accelerating from bench to bedside.

引用

页码：523 / 532

页数：10