One of the most common complications of sickle-cell disease occurs when deformed red blood cells clump together, blocking tiny blood vessels and causing severe pain and swelling in the affected body parts.
A new study from MIT sheds light on how these events, known as vaso-occlusive pain crises, arise. The findings also represent a step toward being able to predict when such a crisis might occur.
“These painful crises are very much unpredictable. In a sense, we understand why they happen, but we don’t have a good way to predict them yet,” says Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and one of the senior authors of the study.
The researchers found that these painful events are most likely to be produced by immature red blood cells, called reticulocytes, which are more prone to stick to blood vessel walls.
Subra Suresh, president of Singapore’s Nanyang Technological University, former dean of engineering at MIT, and the Vannevar Bush Professor Emeritus of Engineering, is also a senior author of the study, which appears in Proceedings of the National Academy of Sciences the week of Sept. 3. The paper’s lead authors are MIT postdoc Dimitrios Papageorgiou and former postdoc Sabia Abidi.
V1: Different types of adherent sickle cells to the microchannel surface under hypoxia (low oxygen) and shear flow, including i) sickle reticulocytes (young red blood cells): a, b; ii) sickle mature red blood cells: d, g, h, i, f; and iii) irreversibly sickled cells: m. (Credit: Courtesy of the researchers)
Simulating blood flow
Patients with sickle cell disease have a single mutation in the gene that encodes hemoglobin, the protein that allows red blood cells to carry oxygen. This produces misshapen red blood cells: Instead of the characteristic disc shape, cells become sickle-shaped, especially in low-oxygen conditions. Patients often suffer from anemia because the abnormal hemoglobin can’t carry as much oxygen, as well as from vaso-occlusive pain crises, which are usually treated with opioids or other drugs.
To probe how red blood cells interact with blood vessels to set off a vaso-occlusive crisis, the researchers built a specialized microfluidic system that mimics the post-capillary vessels, which carry deoxygenated blood away from the capillaries. These vessels, about 10-20 microns in diameter, are where vaso-occlusions are most likely to occur.