Red blood cells
Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.
The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.
The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.
The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.
Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.
With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.
With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.
The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.
Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.
Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a-b-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.
To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.
The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rhnull), Kell (K0), Duffy (Duffynull), and GPB (S-s-U-).
RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.
“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”