Tailoring blood cells to help rare blood group patients

Tailoring blood cells to help rare blood group patients
For some blood transfusion patients, it is particularly difficult to find a compatible blood donor.

Researchers from Ashley Toye and colleagues at the University of Bristol, UK and NHS Blood and Transport are a step closer to growing and tailoring blood cells to the special needs of transfusion patients with rare blood groups.

For some blood transfusion patients, it is particularly difficult to find a compatible blood donor. Growing and tailoring blood cells in the laboratory has long been an overarching goal of scientists for these patients.

When it comes to blood transfusions, it is important to take all different blood groups into account. The immune system can attack any cell presenting an antigen not naturally found on the body’s own cells. Receiving a blood transfusion from an incompatible donor leads to an immune response causing destruction of the red blood cells and can be life-threatening.

Blood group systems

There are 36 different blood group systems to categorise more than 350 antigens that appear on red blood cells in different combinations. The ABO and Rh blood group systems are the most clinically important as they have the most immunogenic antigens.

Before a blood transfusion, the donor and receiver are usually matched according to these two systems. Blood from donors who lack the A, B and RhD antigens is tolerated by most immune systems. But there are exceptions. Individuals who require repeated transfusion over longer time periods are more likely to develop an immune response to minor, less common antigens. In addition, people with very rare blood types require donations from an individual with a more closely matched blood type. These cases pose a major challenge to transfusion services.

The research

Previously, the researchers had already generated a red blood cell precursor cell line, able to be grown, that can be encouraged to generate red blood cells in the laboratory. To meet the needs of transfusion patients at high risk for complication, the researchers now engineered this cell line to express fewer antigens and be less immunogenic.

The researchers first conducted a survey to investigate which antigens most commonly caused challenges in identifying a matched donated unit for patients. They identified five blood group proteins with antigens that were responsible for incompatibility in 48 out of 56 cases.

Next, Toye and colleagues removed these blood groups from their blood cell by genome editing. They created several new cell lines that lacked individual blood groups before creating a single line in which all five were removed.

Red blood cells derived from this line could theoretically serve most of the challenging cases they identified.

Scientists are still a long way from growing and tailoring blood cells in the laboratory at large enough quantities to use them for blood transfusion. However, once the technical hurdles are overcome, the first recipients of these cells will most likely be patients for that it is difficult or impossible to find a donor.

The research of Toye and colleagues shows that it is now possible to tailor the antigenic profile of blood cell lines to the needs of these patients.

Source: EMBO

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