Language
Country/Area
No result found
rom beer to biotech: What are history's weirdest blood substitutes
Blood substitute (also known as artificial blood or blood surrogate) is a substance that simulates and satisfies certain functions of biological blood. These substitutes are designed to provide an alternative to transfusion, the process of transferring blood or blood-based products from one person to another. To date, there is no recognized substitute for oxygen-carrying blood, the typical target of red blood cell transfusions; however, several non-blood volume expanders are commercially available for situations where only fluid restoration is required. These products help doctors and surgeons avoid the risks of disease transmission and immunosuppression while addressing the shortage of blood donors and meeting the needs of those who refuse blood transfusions for religious reasons, such as Jehovah's Witnesses.
Major “oxygen-carrying” blood substitutes include hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon emulsions, while oxygen therapy products are currently undergoing clinical trials in the United States and the European Union.
The history of research on blood substitutes dates back to 1616 when William Harvey discovered the blood circulatory system. Scientists at the time experimented with beer, urine, milk, and non-human animal blood as blood substitutes. Sir Christopher Wren even proposed using wine and opium as alternatives. As modern transfusion medicine developed in the early 20th century, the work of Landstein and co-authors led to the beginning of an understanding of the basic principles of blood typing serology.
Restrictions on blood transfusion medicine in wartime situations, such as during World War II, paved the way for research into blood substitutes.
Early attempts at blood substitutes faced significant side effects that the knowledge and technology available at the time could not eliminate quickly enough. The emergence of AIDS in the 1980s once again stimulated the need to develop safer blood substitutes. With public concerns about blood supply safety and the impact of bovine spongiform encephalopathy, blood donations continue to decline while demand continues to rise. This contradictory situation has created a good environment for the further development of blood substitutes. In 2023, the Defense Advanced Research Projects Agency (DARPA) announced funding for 12 universities and laboratories to conduct research on synthetic blood, with human trials expected to take place between 2028 and 2030.
Development Path
The development of blood substitutes has focused on molecules that can carry oxygen, with major work focusing on recombinant hemoglobin (the molecule that normally carries oxygen) and perfluorocarbons (PFCs). The first approved oxygen-carrying blood substitute was a perfluorocarbon-based product, Fluosol-DA-20, produced by Green Cross Corporation of Japan and approved by the U.S. Food and Drug Administration (FDA) in 1989. Although the product was withdrawn in 1994 due to limited effectiveness, learning difficulties, and side effects, Fluosol-DA remains the only oxygen therapy product to receive full FDA approval.
As of 2017, no hemoglobin-based products have been approved.
Exploration of perfluorocarbons
Perfluorinated chemicals are insoluble in water and do not mix with blood, so an emulsion needs to be made by dispersing small particles of the PFC in water. This fluid is mixed with antibiotics, vitamins, nutrients and salts to create a cocktail of about 80 different components that perform many of the important functions of natural blood. The diameter of PFC particles is about 1/40 of that of red blood cells. This small size enables PFC particles to pass through capillaries where there is no red blood cell flow, which can theoretically provide benefits for damaged, ischemic tissues.
PFC solutions have such a strong oxygen-carrying capacity that even mammals (including humans) can survive breathing liquid PFC solutions. PFCs also offer advantages that do not rely on modified hemoglobin, have unlimited manufacturing capacity, and are capable of heat sterilization and highly efficient oxygen transfer and carbon dioxide removal.
Hemoglobin-based challengesHemoglobin is the major component of red blood cells, accounting for approximately 33% of the cell mass. Hemoglobin-based products are called hemoglobin-based oxygen carriers (HBOCs). Unmodified free hemoglobin is unable to effectively oxygenate tissues because of its high oxygen affinity and its short half-life in blood vessels, which limits its clinical application. To overcome these toxicities, researchers have adopted various approaches such as genetic engineering, cross-linking, polymerization and encapsulation.
The research and development of many hemoglobin-based products has gone through twists and turns. Many products have been discontinued due to increased mortality or safety issues, and none of them have continued to this day.
Possibilities of stem cells
Stem cells offer the possibility of producing transfusionable blood. According to the research of Giarratana et al., hematopoietic stem cells are used for large-scale in vitro production of mature human blood cells. These cultured cells have the same hemoglobin content and morphology as natural red blood cells, and their lifespan is close to that of normal red blood cells.
In 2010, an experimental team at the U.S. Department of Defense began working to create artificial blood for use in remote areas and to more quickly transfuse blood to injured soldiers. The blood is made from hematopoietic stem cells removed from the umbilical cord of a human mother, using a process called "hemotherapy." The technology has been used in the past in animals and plants to mass-produce medical substances, with each umbilical cord producing about 20 units of blood.
After FDA review, this type of blood is found to be safe and meets FDA requirements. If successfully used, the cost per unit will drop from $5,000 to less than $1,000, and it will be compatible with all common blood types.
Today, with the evolution of technology, the prospect of artificial blood seems to be more and more promising, but whether the development of blood substitutes can truly solve the medical challenges we face still requires in-depth consideration?
