THE NEED FOR blood is universal. Several million people receive blood transfusions annually and hundreds of thousands die of blood loss each year. Given the demand, relying solely on the generosity of donors has been challenging.

Scientists and health-care professionals have been exploring blood substitutes for centuries. After the discovery of blood circulation in 1616, people tried various transfusion alternatives such as beer, milk and urine without success.

Research efforts to find blood alternatives have intensified in the past several decades with limited success because of the nature of blood. But recent advances in biomedical engineering, synthetic chemistry and stem cell biology have helped address several limitations and encouraged many more researchers to find viable blood substitutes.

Blood has multiple ingredients. The liquid component is plasma, which contains salts, antibodies and other major proteins. The solid – or cellular – component is a small fraction of platelets (essential for clotting), white blood cells (to fight infections) and an abundance of red blood cells (RBCs). Each RBC encases a special protein called hemoglobin that is essential for transporting oxygen and other gases.

Although donor blood is the best option, it has several limitations. Each unit can be stored for up to only six weeks at cool temperatures, causing challenges for use in emergency situations. Blood cells also have many proteins on their surface that elicit strong immune responses if mismatched during a transfusion and can harbor infectious pathogens.

The ideal prototype of a blood substitute aims to overcome these limitations. Being shelf stable outside hospitals would make it easier for use in urgent situations. A sterile design and manufacturing pipeline would prevent the spread of blood-borne pathogens. But while satisfying every criterion may be difficult, researchers are making significant progress via multidisciplinary approaches.

Other researchers are exploring hemoglobin from the earthworm. Earthworm hemoglobin has many favorable adaptations that makes it a great blood substitute candidate and preliminary studies have shown that they can safely deliver oxygen in mice and hamsters without the adverse effects of cow and human hemoglobin.                       Researchers are also exploiting the flexibility of stem cells. Adult human cells can be turned into multipurpose stem cells, which can then be converted into blood cells.

Despite scientific complexities, research on synthetic blood substitutes is advancing rapidly. FDA supports “the safe clinical development of HBOCs”, and works with industry and scientific groups to advance these products. Once it can establish benefit in clinical settings where blood is not an option and have learned how to extend the circulation time of the artificial oxygen carriers, it is expected that these carriers can be used as a true alternative to natural blood. By Manny Palomar, PhD (EV Mail August 1-7, 2022 issue)