Helping patients and culture more blood

To fit through the thinnest capillaries, red blood cells are able to shrink. Francesca Aglialoro investigates how they do this. It is important for patients with the rare blood disease xerocytosis, as well as for the production of cultured blood. Francesca:

"Red blood cells are very flexible. This allows them to crawl through the smallest capillaries to bring oxygen to the tissues. They play with their volume. If there is little space, they will spit out water, if there is more space, they will take up water. This is a tightly controlled process, for which the cells use special channels that allow salt particles to pass through. As soon as red blood cells 'feel' that they move through narrow blood vessels, they let calcium in. For a good salt balance, water goes out, which makes the cell shrink".

Rare blood disease

"Sometimes things go wrong. Patients with the rare blood disease xerocytosis have a hereditary defect in their calcium channel. It works overtime, which causes the red blood cells to take up too much calcium, shrink and die. As a result, patients suffer from anemia and iron accumulation. I have discovered that you can find the calcium channel not only in the red blood cell, but that it is also active in its predecessor. Remarkable, because this immature cell does not yet flow through the blood vessels. It is stuck in its place in the bone marrow.

Because it is difficult to get bone marrow, I have grown precursor cells from stem cells from the blood of healthy donors and patients with xerocytosis. I investigate the processes a calcium channel induces in the cell and look for differences between donor and patient. Hopefully we can find a way to control the calcium channel in patients in the future".

Culturing blood

"My research has another application, namely in the making of cultured blood from stem cells. For a high yield we use a bioreactor. The culture fluid with the cells in it is stirred in that culture vessel. The propeller causes a kind of turbulence that makes the same calcium channels work harder. As a result, these cells do not grow that fast. By inhibiting the calcium channels, we may be able to increase the yield of cultured blood".

Francesca Aglialoro is conducting her PhD research at Sanquin Research in the Hematopoiesis group, under the supervision of Dr. Emile van den Akker and Dr. Marieke von Lindern.