MINNEAPOLIS / ST. PAUL (02/10/2026) — Researchers at the University of Minnesota Twin Cities have made a significant breakthrough in understanding why patients with the same genetic mutation for sickle cell disease experience varying symptoms. The study, published in Science Advances, suggests that the severity of the disease is more accurately predicted by the behavior of a small population of highly “stiff” red blood cells rather than the average “thickness” of a patient’s blood.
This discovery could explain the differences in pain levels, organ damage, and treatment responses among patients. The stiff cells, which reorganize themselves within the bloodstream, push towards the edges of blood vessels—a process known as margination—creating increased friction and resistance compared to more flexible cells.
Understanding Sickle Cell Disease
Sickle cell disease is a hereditary condition that affects millions globally. It causes red blood cells, which are typically flexible and doughnut-shaped, to become rigid and crescent-shaped in low-oxygen environments. This leads to blockages in blood vessels, severe pain, and a reduced lifespan. Traditionally, medical tests have used “bulk” measurements that average out the properties of all cells, often overlooking the critical differences between individual cells.
“Our work bridges the gap between how single cells behave and how the entire blood supply flows,” said David Wood, a professor in the University of Minnesota Department of Biomedical Engineering and senior author of the study.
“By using an engineering approach to measure both individual cell properties and whole blood dynamics, we found that patients with very different clinical profiles all follow the same underlying physical relationship governed by the fraction of stiff cells.”
Microfluidic Technology and Key Findings
The research team utilized advanced microfluidic “chips” that simulate human blood vessels to identify two primary ways in which blood flow is disrupted:
- Margination: Even a small number of stiff cells can migrate to the vessel walls, significantly increasing wall friction.
- Localized Jamming: At higher concentrations, stiff cells can cause the blood to “jam” in specific areas, leading to a sudden and dramatic increase in flow resistance.
These stiff cells begin to appear at oxygen levels as high as 12 percent, which are typically found in the lungs and brain. This suggests that the physical processes leading to vessel blockages can commence much earlier in the oxygen-depletion process than previously believed.
Implications for Treatment and Future Research
“I am really excited we were able to provide greater insight into the physical mechanisms driving the disease,” said Hannah Szafraniec, a Ph.D. candidate in the University of Minnesota Department of Biomedical Engineering and lead author of the paper.
“This could help the field develop more effective, personalized therapies and new testing for early warning of symptoms.”
This research holds promise for more personalized treatments for sickle cell patients and could lead to new tests for early symptom detection. Moreover, the findings could be applicable to other blood-related disorders, including malaria, diabetes, and certain cancers.
The study was conducted in collaboration with University College of London, University of Edinburgh, Harvard University, Massachusetts General Hospital, and Princeton University. It was funded by the National Heart, Lung, and Blood Institute, a part of the U.S. National Institutes of Health.
The announcement comes as the medical community continues to seek more effective treatments for sickle cell disease, which remains a significant global health challenge. As research progresses, the hope is that these insights will lead to improved quality of life and outcomes for patients worldwide.
