Sickle Cell disease - 3D Illustration of sickled blood cells on a dark background
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Research, led by MIT, shows that a “spleen-on-a-chip” device can accurately model the human spleen and could be used to understand sickle cell disease better and help guide new therapy development.

Sickle cell disease is an inherited blood disorder, thought to affect around 100,000 Americans. The condition manifests as abnormally shaped red blood cells and causes health problems when these cells die, or get stuck sand clog blood flow in smaller blood vessels.

Normally, the spleen removes abnormal blood cells from circulation around the body and triggers the formation of new red blood cells using in built filters. Most red blood cells live for around 120 days, so approximately one percent of the supply has to be removed every day. However, this process can be severely disrupted in sickle cell patients.

The abnormal red blood cells produced by patients with this condition can clog up the spleen’s filters (interendothelial slits) and cause a condition called acute splenic sequestration, which can be life threatening. The abnormal blood cells clog up the spleen and this leads to a drop in the production of new blood cells and a subsequent fall in hemoglobin levels.

As reported in the journal PNAS, Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering, and colleagues have developed an oxygen-mediated, organ-on-a-chip device that is able to model the flow of red blood cells into and out of the spleen and can model acute splenic sequestration.

The device uses microfluidic technology and consists of two modules, the S chip, which mimics the interendothelial slits found in the spleen, and the M chip, which copies the action of macrophage cells. The model spleen also contains a gas channel to allow changing oxygen concentrations as you would see in the body.

The researchers tested blood cells from patients with sickle cell disease as well as healthy controls using the device. They showed that reduced oxygen conditions were linked to faster clogging of the interendothelial slits by sickled blood cells.

“If we increase the oxygen levels, it will reverse the blockage,” explained Dao, one of the senior authors of the study, in a press statement. “This mimics what is done when there’s a splenic sequestration crisis.” Blood transfusions are commonly used to treat sickle cell crises and this may explain why they are helpful, as they bring oxygen into the spleen.

“These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic red blood cell retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and acute splenic sequestration crisis in sickle cell disease and possible clinical manifestations in other hematologic diseases,” conclude the authors.

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