In the midst of persistent national and international blood supply shortages, scientists are diligently working to make the dream of laboratory-made universal donor blood a reality. This achievement could revolutionize transfusion medicine by ensuring a readily available and universally compatible blood supply.
Efforts in this field are progressing along two promising tracks. Some research groups are experimenting with enzymes capable of transforming type A or B blood into type O blood, which can be safely transfused to most individuals. This groundbreaking work has even extended into preclinical studies on creating universal donor organs. Although significant obstacles remain, the progress being made is a glimmer of hope for the healthcare sector.
Proof of Concept: A Step Toward Universal Compatibility
Type A and B blood are distinguished from each other and from the universally compatible type O blood by specific carbohydrate molecules on the surface of red blood cells. Type O blood, considered universal donor blood, has only the core sugar molecule on its surface, enabling it to be safely transfused not only to type O recipients but also to those with types A, B, and AB blood. Mismatched blood transfusions can lead to immune reactions that are potentially life-threatening, making ABO blood type compatibility the bedrock of transfusion services worldwide.
Martin Olsson, a prominent figure in the field of transfusion medicine, highlights that ABO incompatibility is the cause of roughly half of the major complications associated with blood transfusions. The importance of universal donor blood becomes evident in situations when there is no time or resources to determine the recipient’s blood type, which necessitates the use of type O blood.
Additionally, another key factor in blood compatibility is the presence or absence of the Rhesus (Rh) factor protein, determining whether blood type is positive or negative. True universal donor blood is type O negative, a relatively rare blood type used in most emergency transfusions. Given that the majority of people have Rh-positive blood, the demand for O-positive blood is also high. Yet, both forms of type O blood remain in limited supply globally.
In many countries, centralized systems distribute donor blood to hospitals to ensure adequate supplies of each ABO blood group. However, the varying consumption rates at different hospitals create significant logistical challenges. When blood is running low at one facility, rapid resupply is required, while if a blood type is underutilized, it must be redirected to another hospital before expiration. Addressing these challenges necessitates a more abundant supply of universal donor blood.
Sugar Removal Holds the Key
Each red blood cell features approximately 1 million sugar antigens on its surface, and specific genes encode the enzymes responsible for producing these sugars. Enzymes capable of selectively removing these sugars could be the key to converting type A or B blood into type O, thereby increasing the availability of universal donor blood.
In 1982, a pioneering study led by Jack Goldstein at the New York Blood Center demonstrated the use of enzymes derived from green coffee beans to eliminate B-group sugars from red blood cells. They successfully transfused small amounts of converted blood into volunteers without any apparent harm. However, the use of coffee bean enzymes was associated with several limitations, including the need for an acidic pH during the conversion process, inefficiency, and high costs.
Over time, scientists, including Martin Olsson and Stephen Withers, developed more efficient enzymes capable of removing both A and B sugars at a neutral pH. In 2019, a significant breakthrough occurred when Withers and his team identified two gut microbe enzymes that, when used together, could convert type A blood into type O blood approximately 30 times faster than previous methods. The high efficiency of this approach has paved the way for clinical trials and further development.
Furthermore, these enzymes have the potential to convert type A whole blood to universal blood, which is of particular interest to the U.S. military for transfusions in combat situations, as whole blood is associated with better outcomes. The military has provided a $5 million grant to develop a filter that removes the enzymes from converted universal whole blood, ensuring safety for patients.
Enzymatic Conversion for Organ Transplants
Scientists have also explored the possibility of using these enzymes to convert donor organs from blood type A to universal donor organs. Preliminary experiments conducted on donor lungs and kidneys have shown promise. Converting organs to a universal blood type could remove the necessity of matching the ABO blood type, significantly improving the chances of successful transplantation. While organs will eventually produce new sugars, existing immunomodulation regimens may manage this issue.
The development of universal donor organs presents a significant advancement in the field of transplantation medicine, potentially saving countless lives by broadening the pool of available organs.
New Discoveries in Enzyme Efficiency
More recent studies, led by Marco Moracci at the University of Naples, have identified three bacterial enzymes with superior efficiency in converting blood type A into universal type O blood when compared to currently available enzymes. This research holds promise for the optimization of the enzymatic conversion process.
Additionally, a group at the University of Bristol is exploring the cultivation of red blood cells from stem cells in the laboratory. Manufactured blood may be beneficial for individuals who require frequent transfusions, such as those with inherited anemia. Unlike normal donor blood, which contains red blood cells at different life stages, including those close to expiration, laboratory-grown blood cells could potentially reduce the frequency of transfusions, improving patient outcomes and reducing the burden on healthcare systems.
Challenges and the Road Ahead
Despite the remarkable progress in the development of laboratory-made universal donor blood, several critical challenges remain. Ensuring the safety of these new blood products is paramount. Researchers must confirm that removing surface sugars from red blood cells does not weaken or damage the cells, potentially causing life-threatening complications.
Additionally, researchers must address potential immune reactions in patients receiving these blood products. Even small traces of A or B sugars left on the cells or remnants of the bacterial enzymes used in the conversion process could trigger immune responses.
Retrospective analyses have raised questions about the safety of giving type O blood to individuals with different blood types, as this practice may lead to worse patient outcomes, potentially undermining the concept of universal blood. Clinical trials, like the one conducted by Rebecca Barty and her colleagues at McMaster University, are essential to evaluate the safety and efficacy of new universal blood products comprehensively.
The quest for laboratory-made universal donor blood faces substantial challenges, but its success would fulfill a critical need in healthcare. If researchers can clear these hurdles and establish both short-term and long-term safety in clinical trials, they could finally achieve the long-sought-after “holy grail” of universal donor blood, a development that would revolutionize transfusion medicine.
Source: JAMA Network Open Journal