Modified blood cells successfully transfused between species

A study by an international research group reveals a surprising blood modification method that not only protects red blood cells for cryopreservation of transplanted organs by perfusion, but could also make blood types compatible with each other and eventually allow blood transfusions between species. The breakthrough is reported in the Proceedings of the National Academy of SciencesAnd if the study’s claims are confirmed, this development could have a resounding impact in the clinical field.

In January 2024, the American Red Cross declared an emergency blood shortage, reporting the lowest number of blood donations in 20 years. Estimating a 40% decline in donors over two decades, the Red Cross noted several contributing factors, including COVID-19, which has curtailed workplace blood drives, as well as changes to transfusion protocols in hospitals. The growing need to increase blood supply is now driving technological approaches, including advances in blood preservation and storage.

The researchers in the new study describe a biocompatible blood silicification method, which they call SARNAS (Shielding-augmenting RBC-in-nanoscale amorphous silica), or RBC-in-nanoscale amorphous silica for short. The technique involves surface engineering and structural augmentation of red blood cells, essentially giving them nanoscale silica-based exoskeletons. They conducted a number of in vivo studies and reported excellent biocompatibility, as well as 100% cryoprotection under storage conditions.

But the most interesting thing is that SARNAS protects the surface antigens of red blood cells, i.e. the proteins, glycolipids and carbohydrates that distinguish blood groups. This means that Si red blood cells escape immune detection and could serve as universal blood that can be transfused between people of different blood groups, or even between species. The authors write: “The presented method offers a simple, efficient and cost-effective approach to developing universal blood.”

The authors sought to address a specific medical application: the perfusion of donor organs for cryopreservation prior to transplantation. Artificial perfusion, a technique of artificial perfusion used for this purpose, involves pumping an oxygenated solution through the donor organs to mimic natural blood flow. Perfusion also controls the temperature of the organ to preserve it prior to transplantation.

The use of artificial perfusion solutions is widespread, but the best perfusion fluid is of course blood. Unfortunately, using blood to preserve organs has disadvantages, including the short shelf life of red blood cells and the resulting waste, blood group incompatibility, and mechanical damage to cells during perfusion.

In tests, Si-RBCs provided universal blood compatibility, performed exactly like normal red blood cells in mechanical perfusion tests, including cell mechanical deformability and oxygen transport, and maintained their membrane and structural integrity.

Xenotransfusion

To confirm the safety of Si-RBCs between cross-species blood transfusions, the researchers conducted two tests on mice. One group received a transfusion of normal human RBCs, while the test group received the Si-RBCs. The transfused volume was 4% of the total blood volume, which is the medical definition of a blood transfusion. Compared to the human RBC group, the Si-RBC mice showed negligible measures of damage to key organs, including the kidneys and liver.

In the second test, both groups of mice received transfusions of 20% of the total blood volume. The authors write: “Both the Si RBC group and the control group showed normal physiological behavior and good biosafety when the transfusion volume was 20%, while the native RBC group showed signs of liver damage and inflammation… All these results confirm that Si RBCs not only evade immune activation in different species, but also function perfectly for oxygen transport.”

They conclude that the technique of creating an exoskeleton around red blood cells provides an innovative experimental basis for interspecies blood transfusion and could potentially alleviate blood supply shortages in the future.

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