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Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip. Cell Death Dis 2018 Feb 14;9(2):223

Date

02/16/2018

Pubmed ID

29445080

Pubmed Central ID

PMC5833800

DOI

10.1038/s41419-018-0304-8

Scopus ID

2-s2.0-85042066061 (requires institutional sign-in at Scopus site)   156 Citations

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.

Author List

Jalili-Firoozinezhad S, Prantil-Baun R, Jiang A, Potla R, Mammoto T, Weaver JC, Ferrante TC, Kim HJ, Cabral JMS, Levy O, Ingber DE

Author

Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acids, Dicarboxylic
Animals
Apoptosis
Caco-2 Cells
Cells, Cultured
DNA Fragmentation
Gamma Rays
Human Umbilical Vein Endothelial Cells
Humans
Intestinal Mucosa
Lab-On-A-Chip Devices
Lipid Peroxidation
Models, Biological
Permeability
Radiation Injuries
Radiation-Protective Agents
Reactive Oxygen Species
Tight Junctions