Fu Guoxiang,Li Yuanchuang,Pan Mengxue,Guo Qiang,Rao Xinxin,Xu Xiaoya,Zhou Yi,Shao Chunlin,Gao Jianjun,Hua Guoqiang.Establishment of an intestinal organoid-based method to investigate the radiation mitigation effect of Epiregulin[J].Chinese Journal of Radiological Medicine and Protection,2018,38(9):641-646
Establishment of an intestinal organoid-based method to investigate the radiation mitigation effect of Epiregulin
Received:March 29, 2018  
DOI:10.3760/cma.j.issn.0254-5098.2018.09.001
KeyWords:Intestinal stem cell  Intestinal Organoid  Radiation  Epiregulin  Radiation-induced gastrointestinal syndrome
FundProject:国家自然科学基金(31470826,31670858)
Author NameAffiliationE-mail
Fu Guoxiang Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Li Yuanchuang Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Pan Mengxue Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Guo Qiang Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Rao Xinxin Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Xu Xiaoya Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Zhou Yi Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Shao Chunlin Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Gao Jianjun Institute of Radiation Medicine, Fudan University, Shanghai 200032, China  
Hua Guoqiang Institute of Radiation Medicine, Fudan University, Shanghai 200032, China guoqianghua@fudan.edu.cn 
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Abstract::
      Objective To establish an intestinal organoid-based assay to investigate the radiation mitigation effect of epiregulin in vitro. Methods Intestinal crypts were released from tissue incubated with EDTA. Intestinal crypts seeded in 3D matrigel were irradiated at 24 h after plating. The radiation mitigation effect of epiregulin was evaluated by measuring the survival rate, size and budding numbers of the organoid after irradiation, and the basic FGF was used as a positive control of epiregulin. Results Radiation-induced lethality and dose-dependent survival curve of the intestinal organoid were consistent with in vivo data. Treatment with epiregulin (400 ng/ml) at 24 h post-radiation significantly increased survival rate of 8 Gy X-ray irradiated intestinal organoid in comparison with non-treated group[(12.56±1.02)% vs. (4.73±0.38)%, t=12.43,P<0.05]. Conclusions Epiregulin has radiation mitigation effect on intestinal organoid and could serve as a potential medical countermeasure to mitigate gastrointestinal toxicity.
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