While researchers have made incredible improvements in treating sickle cell disease over the last 50 years, there are still major questions about how the deadly condition affects the body. Some of those answers, however, may come from an unexpected field: fluid dynamics.
In November 2019, Michael Graham, Vilas Distinguished Achievement Professor and Harvey D. Spangler Professor in chemical and biological engineering, exemplified how researchers in engineering and medicine are teaming up to understand the disease during the inaugural William R. Schowalter lecture at the AIChE annual meeting in Orlando.
Sickle cell disease is a disorder of red blood cells that affects 70,000 to 80,000 Americans per year, primarily African Americans and Hispanic Americans. In the disorder, as the cells age, they stiffen and take on a moon-like, or sickle shape. This leads to all sorts of complications, including anemia, since the cells break down more quickly, reducing oxygen carrying capacity. The cells can also get stuck in small blood vessels, leading to organ damage and chronic inflammation.
The disease is often painful and the long-term outlook is not good. In the 1970s, the average lifespan for a person with sickle cell was 14 years. Today, with advancing treatments, people often live into their 40s. But there is still more progress to be made.
Over the last decade, Graham’s research group has developed mathematical models to understand how different types of cells circulate in the bloodstream. What they’ve found is that stiffer cells, like white blood cells and platelets, tend to collide with red bloods cells while circulating through the body, which drives them toward the walls of the blood vessels.
Building on that knowledge, Graham and collaborator Wilbur Lam, an MD and biomedical engineer at Georgia Tech and Emory University, have hypothesized that this process, called “margination,” is also at play in sickle cell disease. In experimental observations, Lam found that there’s evidence of damage to the cells lining blood vessels in the disease, possibly caused by the stiff, scythe-like cells congregating near the walls.
To confirm this hypothesis, Graham modeled how the sickle cells behave in an idealized model of blood vessels. Using mathematical models of flow systems, he created a detailed simulation of how the cells deform and collide with one another during blood flow. “Sickle cells are stiffer than healthy cells and as they move through the bloodstream they get pushed by the softer, more normal cells toward the walls and that causes damage,” he says. “We can actually look in the mathematical model how these disease cells generate stresses that might damage the blood vessel walls.”
While the models are simpler then the incredibly complex network of arteries and veins in a human circulatory system, Graham says the simulations still show how margination of the sickle cells could cause damage. “We’re trying to keep things simple enough that you can actually make progress in addressing some hypothesis,” he says.
The hope is that the finding will eventually help researchers understand and find new treatment methods for the disease. Graham says he and Lam recently submitted a paper on the research which they hope will be published soon.
“There’s still lots of work to be done, but it’s kind of an exciting direction for sure, and something that hadn’t been addressed previously,” Graham says. “One cool thing about it is that it’s the kind of thing that really comes about from the interaction of someone who knows about fluid mechanics and someone who knows about medicine. I think that was a very interesting aspect of this.”
Author: Jason Daley