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Published on: January 3, 2025
Identifying Candidate Biomarkers of Ionizing Radiation in Human Pulmonary Microvascular Lumens Using Microfluidics-A
Larry J Millet1, Richard J Giannone2, Michael S Greenwood3
1The Center for Environmental Biotechnology, The University of Tennessee, Knoxville, TN 37996, USA.
Abstract:
The microvasculature system is critical for the delivery and removal of key nutrients and waste products and is significantly damaged by ionizing radiation. Single-cell capillaries and microvasculature structures are the primary cause of circulatory dysfunction, one that results in morbidities leading to progressive tissue and organ failure and premature death. Identifying tissue-specific biomarkers that are predictive of the extent of tissue and organ damage will aid in developing medical countermeasures for treating individuals exposed to ionizing radiation. In this pilot study, we developed and tested a 17 µL human-derived microvascular microfluidic lumen for identifying candidate biomarkers of ionizing radiation exposure. Through mass-spectrometry-based proteomics, we detected 35 proteins that may be candidate early biomarkers of ionizing radiation exposure. This pilot study demonstrates the feasibility of using humanized microfluidic and organ-on-a-chip systems for biomarker discovery studies. A more elaborate study of sufficient statistical power is needed to identify candidate biomarkers and test medical countermeasures of ionizing radiation.
Insights
Ionizing radiation damages microvasculature, causing organ failure. This study used microfluidics to find 35 potential early biomarkers for radiation exposure, aiding future medical countermeasures.
Area of Science:
- Biomedical Engineering
- Radiation Biology
- Proteomics
Background:
- The microvasculature is vital for nutrient/waste transport and is susceptible to ionizing radiation damage.
- Radiation-induced microvascular damage leads to circulatory dysfunction, tissue failure, and premature death.
- Early detection of radiation damage requires identifying specific biomarkers.
Purpose of the Study:
- To develop and test a human microvascular microfluidic system for identifying biomarkers of ionizing radiation exposure.
- To discover candidate early biomarkers predictive of radiation-induced tissue damage.
Main Methods:
- Developed a 17 µL human-derived microvascular microfluidic lumen.
- Utilized mass-spectrometry-based proteomics to analyze protein expression.
- Compared protein profiles in irradiated versus non-irradiated samples.
Main Results:
- Identified 35 proteins as potential early biomarkers of ionizing radiation exposure.
- Demonstrated the feasibility of using microfluidic organ-on-a-chip systems for biomarker discovery.
- Showcased the system's ability to detect radiation-induced proteomic changes.
Conclusions:
- Human microfluidic systems are effective for early biomarker discovery after radiation exposure.
- The identified proteins warrant further investigation as diagnostic markers.
- This approach can accelerate the development of medical countermeasures for radiation injury.
