Developing an RNA Signature for Radiation Injury Using a Human Liver-on-a-Chip Model DOI
Shannon Martello, Youki Ueda, Michelle A. Bylicky

et al.

Radiation Research, Journal Year: 2024, Volume and Issue: 202(3)

Published: Aug. 2, 2024

Radiation exposure in a therapeutic setting or during mass casualty event requires improved medical triaging, where the time to delivery and quantity of countermeasures are critical survival. Radiation-induced liver injury (RILI) fibrosis can lead death, but clinical symptoms manifest late disease pathogenesis there is no simple diagnostic test determine RILI. Because animal models do not completely recapitulate symptoms, we used human liver-on-a-chip model identify biomarkers The goals this study were: 1. establish microfluidic device as physiologically relevant for studying radiation-induced tissue damage; 2. acute changes RNA expression biological pathway regulation that potential mechanisms To functional tissue, Emulate organ-on-a-chip system co-culture sinusoidal endothelial cells (LSECs) hepatocytes. chips were subject 0 Gy (sham), 1 Gy, 4 10 irradiation collected at 6 h, 24 7 days postirradiation isolation. significant messenger (mRNA) long non-coding (lncRNA), performed sequencing (RNASeq) conduct whole transcriptome analysis. We found distinct differences patterns by time, dose, cell type, with higher doses radiation resulting most pronounced changes, anticipated. Ingenuity Pathway Analysis indicated inhibition viability h after LSECs activation hepatocytes, highlighting between types despite receiving same dose. Overall, hepatocytes showed fewer gene response radiation, only 3 statistically differentially expressed genes days: APOBEC3H, PTCHD4, GDNF. further highlight lncRNA interest including DINO PURPL TMPO-AS1 PRC-AS1 LSECs, identifying demonstrated utility primary organ-specific injury, establishing countermeasure development biomarker validation. Furthermore, identified differentiate dose defined cell-specific targets mitigation therapies.

Language: Английский

Developing an RNA Signature for Radiation Injury Using a Human Liver-on-a-Chip Model DOI
Shannon Martello, Youki Ueda, Michelle A. Bylicky

et al.

Radiation Research, Journal Year: 2024, Volume and Issue: 202(3)

Published: Aug. 2, 2024

Radiation exposure in a therapeutic setting or during mass casualty event requires improved medical triaging, where the time to delivery and quantity of countermeasures are critical survival. Radiation-induced liver injury (RILI) fibrosis can lead death, but clinical symptoms manifest late disease pathogenesis there is no simple diagnostic test determine RILI. Because animal models do not completely recapitulate symptoms, we used human liver-on-a-chip model identify biomarkers The goals this study were: 1. establish microfluidic device as physiologically relevant for studying radiation-induced tissue damage; 2. acute changes RNA expression biological pathway regulation that potential mechanisms To functional tissue, Emulate organ-on-a-chip system co-culture sinusoidal endothelial cells (LSECs) hepatocytes. chips were subject 0 Gy (sham), 1 Gy, 4 10 irradiation collected at 6 h, 24 7 days postirradiation isolation. significant messenger (mRNA) long non-coding (lncRNA), performed sequencing (RNASeq) conduct whole transcriptome analysis. We found distinct differences patterns by time, dose, cell type, with higher doses radiation resulting most pronounced changes, anticipated. Ingenuity Pathway Analysis indicated inhibition viability h after LSECs activation hepatocytes, highlighting between types despite receiving same dose. Overall, hepatocytes showed fewer gene response radiation, only 3 statistically differentially expressed genes days: APOBEC3H, PTCHD4, GDNF. further highlight lncRNA interest including DINO PURPL TMPO-AS1 PRC-AS1 LSECs, identifying demonstrated utility primary organ-specific injury, establishing countermeasure development biomarker validation. Furthermore, identified differentiate dose defined cell-specific targets mitigation therapies.

Language: Английский

Citations

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