A team of Chinese scientists has developed a gelatinous “jacket” that camouflages red blood cells and may protect them from a patient’s immune system, according to a study published Saturday in the journal Science Advances. If further research is successful, it could present a solution for people with rare blood types who require transfusions.
Human blood can be categorized into the A, B, AB, and O groups. Each type is defined by a unique set of structures called antigens on the surface of red blood cells: Type A blood has A antigens, type B has B antigens, type AB has both antigens, and type O has neither.
Each of the four classes can be further divided into two groups based on the presence of another antigen, rhesus D (RhD). People who have RhD on their red blood cells are RhD-positive, while those who don’t are RhD-negative.
The body’s immune system uses antigens to detect invaders. If a type A person is transfused with type B blood, their immune system would recognize the foreign antigens and give a seek-and-destroy order. The same principle applies to RhD antigens.
RhD-negative blood is rare, and is sometimes referred to in China as “panda blood.” Although frequency varies by race and ethnicity, between 0.5% and 15% of the world’s population have RhD-negative blood. A 2017 survey indicated that about 1% of Chinese people are RhD-negative.
Consequently, there is a chronic shortage of RhD-negative blood in hospitals and blood banks. In 2017, Sixth Tone reported that many Chinese people with this unusual blood type turn to the black market when they need transfusions.
Scientists have been trying to create universal blood cells that lack these identifying antigens. Previously, they had used enzymes to remove the A and B antigens on blood cells, effectively turning the altered blood cells into type O. However, RhD antigens are tightly bound to the cells’ surface, and excising them with enzymes would inevitably cause the blood cells to burst. Gene-editing has also been considered, but this method could lead to undesirable mutations and has not yet been tested on living organisms.
For Saturday’s study, a team at Zhejiang University in the eastern Chinese city of Hangzhou synthesized a hydrogel material capable of covering RhD antigens without disrupting the red blood cells’ normal functions. Trials in mice showed that these engineered cells could transport oxygen and circulate within the animal just like unaltered blood cells.
To test the hydrogel’s performance in camouflaging RhD antigens, the team injected the coated cells into rabbits whose immune systems had been manipulated to detect RhD. Researchers observed no RhD-specific immune responses in these rabbits — the same result as when they transfused the rabbits with real RhD-negative blood.
“To my knowledge, this is the first time an engineered RhD-negative blood cell showed promising results in animal models,” Wang Ben, a co-author of the paper, told Sixth Tone. “Our material could provide a new technique to address the clinical need for rare blood.”
Wang said that more studies are needed before the hydrogel material can be used in humans, a sentiment echoed by other experts.
“The results presented here are very positive,” Jay Kizhakkedathu, a pathologist at the University of British Columbia, told Sixth Tone. “But some of the ingredients used in making this material could generate free radicals that can damage cells and tissues. Further studies on its toxicity should be conducted.”
The material also has the potential to create universal blood cells lacking all antigens including A, B, and other Rh factors, Wang said.
“Different antigens have different structures and sizes — so in theory, we could further optimize the thickness and texture of our hydrogel to make one that could mask all antigens,” Wang said. “But of course we are still in the very first steps toward making universal blood cells.”