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Cell Death Dis. 2018 Feb 14;9(2):223. doi: 10.1038/s41419-018-0304-8.

Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip.

Author information

1
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
2
Department of Bioengineering and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
3
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
4
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
5
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu.
6
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu.
7
Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USA. don.ingber@wyss.harvard.edu.

Abstract

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.

PMID:
29445080
PMCID:
PMC5833800
DOI:
10.1038/s41419-018-0304-8
[Indexed for MEDLINE]
Free PMC Article

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