The magic of the world’s rarest blood type

Other researchers are also racing to make Rh null blood in the laboratory.

In 2021, immunologist Gregory Denomme and colleagues at the Versiti Blood Research Institute, in Milwaukee, US, used Crispr-Cas9 gene editing technology to create customised rare blood types including Rh null from human induced pluripotent stem cells (hiPSC). These stem cells have properties similar to embryonic stem cells and have the potential to become any cell in the human body, given the right conditions.

Other scientists are using another type of stem cells that are already preprogrammed to become blood cells but haven’t determined which kind yet. For example scientists at Laval University in Quebec, Canada recently extracted blood stem cells from donors with A positive blood. They then used Crispr-Cas9 technology to delete the genes coding for the A and Rh antigens, producing O Rh null immature red blood cells. Researchers in Barcelona, Spain, also recently took stem cells from a Rh null blood donor, and used Crispr-Cas9 to convert their blood from type A to type O, making it more universal.

Nevertheless, despite these impressive efforts it’s important to say that creating artificial lab-grown blood on a scale where people could use it is still a long way off. One difficulty is to get the stem cells to grow into mature red blood cells. In the body, red blood cells are produced from stem cells in the bone marrow, which produces complex signals to guide how they develop. This is difficult to replicate in the laboratory. 

“There is the added problem that when creating Rh null or any other null blood type, the growth and maturation of the red blood cells can be perturbed,” says Denomme, who is now working as a medical affairs director at Grifols Diagnostic Solutions, a healthcare company which specialises in transfusion medicine. “Producing specific blood group genes might result in the cell membrane falling apart, or a loss of producing red blood cells efficiently in cell culture.”


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