MINNEAPOLIS / ST. PAUL (02/10/2026) — A groundbreaking study from the University of Minnesota Twin Cities has unveiled a potential explanation for the varying severity of symptoms experienced by patients with sickle cell disease, despite sharing the same genetic mutation. The research, published in Science Advances, suggests that the key lies not in the average thickness of a patient’s blood, but in the behavior of a small subset of highly “stiff” red blood cells.
These stiff cells have been observed to reorganize within the bloodstream, moving to the edges of blood vessels in a process known as margination. This behavior creates more friction and resistance compared to their flexible counterparts, which could significantly impact the severity of symptoms such as pain and organ damage.
Understanding Sickle Cell Disease
Sickle cell disease is an inherited disorder affecting millions globally. It causes red blood cells, which are typically flexible and doughnut-shaped, to become stiff and crescent-shaped under low-oxygen conditions. This transformation leads to blockages in blood vessels, causing severe pain and reducing life expectancy. Traditionally, blood tests have focused on “bulk” measurements, averaging the properties of all cells and often overlooking critical differences between individual cells.
David Wood, a professor in the University of Minnesota’s Department of Biomedical Engineering and senior author of the study, explained, “Our work bridges the gap between how single cells behave and how the entire blood supply flows. 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.”
Innovative Research Methods
The research team employed advanced microfluidic “chips” that simulate human blood vessels to uncover 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 blood to “jam” in specific areas, leading to a sudden and dramatic increase in flow resistance.
Remarkably, these stiff cells begin to appear at oxygen levels as high as 12 percent, which are typically found in the lungs and brain. This finding suggests that the physical processes leading to vessel blockages can initiate much earlier in the oxygen-depletion process than previously understood.
“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 and lead author of the study. “This could help the field develop more effective, personalized therapies and new testing for early warning of symptoms.”
Implications for Treatment and Future Research
This research could pave the way for more personalized treatments for sickle cell patients and the development of new tests for early symptom detection. Furthermore, the findings may have broader applications, potentially benefiting the understanding and treatment of other blood-related disorders, such as malaria, diabetes, and certain cancers.
The study was a collaborative effort involving researchers from University College London, the University of Edinburgh, Harvard University, Massachusetts General Hospital, and Princeton University. It was funded by the National Heart, Lung, and Blood Institute, part of the U.S. National Institutes of Health.
As the scientific community continues to explore the implications of these findings, the hope is that they will lead to significant advancements in the management and treatment of sickle cell disease, offering new hope to millions affected by the disorder worldwide.
