Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase-expressing umbilical cord mesenchymal stromal cells

被引:19
作者
Gan, Jingyi [1 ]
Meng, Fanwei [1 ]
Zhou, Xin [1 ]
Li, Chan [1 ]
He, Yixin [1 ]
Zeng, Xiaoping [1 ]
Jiang, Xingen [1 ]
Liu, Jia [1 ]
Zeng, Guifang [1 ]
Tang, Yunxia [1 ]
Liu, Muyun [1 ]
Mrsny, Randall J. [3 ,4 ]
Hu, Xiang [1 ]
Hu, Jifan [2 ,3 ]
Li, Tao [1 ]
机构
[1] Shenzhen Beike Cell Engn Res Inst, Shenzhen 518057, Peoples R China
[2] Stanford Univ, Sch Med, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA
[3] GMR Epigenet, Palo Alto, CA USA
[4] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England
基金
美国国家卫生研究院;
关键词
acute radiation syndrome; apoptosis; hematopoietic failure; stem cell; superoxide dismutase; umbilical cord mesenchymal stromal cells; TOTAL-BODY IRRADIATION; INDUCED LIVER-INJURY; STEM-CELLS; BONE-MARROW; OXIDATIVE STRESS; ADIPOSE-TISSUE; PROTECTS; MICE; DELIVERY; THERAPY;
D O I
10.1016/j.jcyt.2014.11.011
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background aims. Acute radiation syndrome (ARS) leads to pancytopenia and multi-organ failure. Transplantation of hematopoietic stem cells provides a curative option for radiation-induced aplasia, but this therapy is limited by donor availability. Methods. We examined an alternative therapeutic approach to ARS with the use of human extracellular superoxide dismutase (ECSOD)-modified umbilical cord mesenchymal stromal cells (UCMSCs). This treatment combines the unique regenerative role of UCMSCs with the anti-oxidative activity of ECSOD. Results. We demonstrated that systemically administered ECSOD-UCMSCs are able to protect mice from sub-lethal doses of radiation and improve survival by promoting multilineage hematopoietic recovery. The therapeutic effect of this treatment is related to the decrease in radiation-induced O-2(-) and apoptosis. Conclusions. Our data highlight the clinical potential of this two-pronged approach to the treatment of ARS, thereby serving as a rapid and effective first-line strategy to combat the hematopoietic failure resulting from a radiation accident, nuclear terrorism and other radiologic emergencies.
引用
收藏
页码:403 / 417
页数:15
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