Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip.
Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip.
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DOI：
10.1038/s41419-018-0304-8
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发表时间：
2018-02-14
影响因子：
9
通讯作者：
Ingber DE
中科院分区：
文献类型：
--
作者：
Jalili-Firoozinezhad S;Prantil-Baun R;Jiang A;Potla R;Mammoto T;Weaver JC;Ferrante TC;Kim HJ;Cabral JMS;Levy O;Ingber DE
对急性暴露在γ辐射下的人类肠道损伤的研究通常依赖于动物模型的使用，因为培养系统不能忠实地模拟人类的肠道生理。在这里，我们使用了一种由人肠上皮细胞和血管内皮细胞组成的人肠道芯片(Gut-on-a-Chip)微流控装置来模拟辐射损伤，并在体外评估辐射对抗药物的疗效。肠道芯片暴露在γ辐射下会导致活性氧的产生、细胞毒性、细胞凋亡和DNA片段化，以及绒毛钝化、紧密连接破坏和肠道屏障完整性的破坏。相比之下，一种潜在的预防性辐射对抗药物二甲氧丙酰甘氨酸(DMOG)的预治疗显著抑制了所有这些损伤反应。因此，除了筛选新的放射防护医学对策药物外，人体肠道芯片还可以作为研究辐射诱导的细胞死亡和相关的胃肠道急性综合征的体外平台。
Studies on human intestinal injury induced by acute exposure to γ-radiation commonly rely on use of animal models because culture systems do not faithfully mimic human intestinal physiology. Here we used a human Gut-on-a-Chip (Gut Chip) microfluidic device lined by human intestinal epithelial cells and vascular endothelial cells to model radiation injury and assess the efficacy of radiation countermeasure drugs in vitro. Exposure of the Gut Chip to γ-radiation resulted in increased generation of reactive oxygen species, cytotoxicity, apoptosis, and DNA fragmentation, as well as villus blunting, disruption of tight junctions, and compromise of intestinal barrier integrity. In contrast, pre-treatment with a potential prophylactic radiation countermeasure drug, dimethyloxaloylglycine (DMOG), significantly suppressed all of these injury responses. Thus, the human Gut Chip may serve as an in vitro platform for studying radiation-induced cell death and associate gastrointestinal acute syndrome, in addition to screening of novel radio-protective medical countermeasure drugs.
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影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
影响因子：
2.2
作者：
Booth C;Tudor G;Tudor J;Katz BP;MacVittie TJ
通讯作者：
MacVittie TJ
DOI：
10.1073/pnas.0504830102
发表时间：
2005-09-13
影响因子：
11.1
作者：
Crawford, PA;Gordon, JI
通讯作者：
Gordon, JI
小鼠粘蛋白基因缺陷会损害宿主对肠道寄生虫感染的抵抗力。
影响因子：
29.4
作者：
Hasnain SZ;Wang H;Ghia JE;Haq N;Deng Y;Velcich A;Grencis RK;Thornton DJ;Khan WI
通讯作者：
Khan WI
影响因子：
--
作者：
François A;Milliat F;Guipaud O;Benderitter M
通讯作者：
Benderitter M