Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip.
Cell Death Dis
; 9(2): 223, 2018 02 14.
Article
en En
| MEDLINE
| ID: mdl-29445080
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Traumatismos por Radiación
/
Protectores contra Radiación
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Dispositivos Laboratorio en un Chip
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Rayos gamma
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Aminoácidos Dicarboxílicos
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Modelos Biológicos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos