SUMMARY:
UCLA researchers in the Department of Medicine and Bioengineering have developed a novel microfluidic approach to study SARS-CoV-2 infection entry into blood cells of COVID-19 patients as a research tool to better understand the mechanisms that lead to blood clot formation.
BACKGROUND:
The World Health Organization estimates that there are over 244 million confirmed worldwide SARS-CoV-2 infection, or COVID-19, cases as of October 2021. SARS-CoV-2 initially infects respiratory epithelial cells, but accompanying this initial infection is the development of abnormal blood clots in some patients, which according to the NIH can be found even in the smallest blood vessels and throughout the body. Early studies on patients who had recovered from COVID-19 revealed abnormalities in the endothelial cells that line blood vessels. Furthermore, the damage caused by viral infection in these endothelial cells can result in elevated numbers of blood clots. Blood clotting is a serious complication of COVID-19 infection as it can lead to organ damage, strokes and heart attacks when left untreated.
Current methods to study the blood vessels damage in COVID-19 patients are limited to retrospective data, and the use of time-consuming and facility-specific animal model studies that make use of the live SARS-CoV2 virus. Microfluidic diagnostic chips have seen application in studies with blood, such as for blood typing and universal coagulation assays because they maintain the relevant physiological flow of the cells and allow for high-throughput studies to be performed. Unfortunately, there are no microfluidic based methods that enable studying SARS-CoV-2 infection in cell types implicated in clotting; lab-on-a-chip methods involving SARS-CoV-2 are currently limited to RNA detection methods. Advancing on these existing technologies could allow more high-throughput studies concerning the viral infection mechanism of SARS-CoV-2 into blood vessel endothelial cells. Novel and physiologically compatible microfluidic chips are needed to model SARS-CoV-2 infection to elucidate mechanisms that cause blood clot formation in patients.
INNOVATION:
Researchers at UCLA led by Dr. Tzung Hsiai have developed a safe and efficient method making use of a microfluidic chip that models SARS-CoV-2 entry. The method involves two components: SARS-CoV-2 mimicking liposomal nanoparticles, and a microfluid chip coated with human endothelial cells. The innovative method recapitulates interaction between human endothelial tissue that lines blood vessels and the viral S-spike protein or spike variants. The S-spike protein then binds to the ACE2 cell surface receptors and is internalized by the endothelial cells. In this manner, the physiological nature of the virus entering the cells can be studied under relevant physiological flow. This technology is useful in modeling and understanding COVID-19 infection in blood vessels of patients that can lead to the formation of blood clots, and for potentially testing novel therapies that interfere with SARS-CoV-2 infection. Importantly, the novel methodology does not require the stringent biosafety level associated with working with live SARS-CoV-2 virus and variants.
POTENTIAL APPLICATIONS:
• Advance the understanding of SARS-CoV-2 infection in endothelial cells.
• Understand SARS-CoV-2 related blood clot formation.
• Test new modalities to interfere with SARS-CoV-2 infection.
ADVANTAGES:
• High throughput method of mimic the entry of SARS-CoV-2.
• Potential cost-effective strategy to test novel COVID-19 therapies.
• Patient-specific blood clot understanding.
DEVELOPMENT-TO-DATE:
UCLA researchers have demonstrated an increase in blood clot formation after human endothelial cells were presented with the Spike protein.
Related Papers (from the inventors only):
Satta, S., Lai, A., Cavallero, S., Williamson, C., Chen, J., Blázquez-Medela, A. M., Roustaei, M., Dillon, B. J., Ashammakhi, N., Carlo, D. D., Li, Z., Sun, R., Hsiai, T. K. Rapid Detection and Inhibition of SARS-CoV-2-Spike Mutation-Mediated Microthrombosis. Advanced Science. 2021.