Looking for the holy grail of science: artificial blood or the first major breakthrough in decades March 24, 2017 Source: WuXi PharmaTech Dr. Doctor is a researcher at Washington University in St. Louis and a child emergency doctor. This is one of his laboratory's recent preclinical studies of artificial blood, and if they are lucky enough, they may rewrite the ups and downs of human failure in the field of artificial blood research for decades. In the United States, approximately 45 million people need blood transfusions each year. Deaths caused by traumatic blood loss can reach tens of thousands. Even if the injured survive, they will often cause permanent damage to the tissue due to oxygen depletion. Once the artificial blood is successfully researched, it can meet the growing demand for clinical blood and play an important role in trauma treatment and surgery. In addition, artificial blood can reduce the difficulty of using blood. At present, whole blood is not easy to obtain and preserve. Fresh blood can only be refrigerated for 42 days, and can only be stored for several hours without being refrigerated. Therefore, in the absence of blood transfusion conditions, such as battlefields, rural areas and car accident scenes, artificial blood can be used as an emergency means to reduce the mortality rate before patients are sent to hospitals, and become an important choice for saving lives. Artificial blood can also improve the level of medical services. For people who need blood transfusions for a long time, such as patients with myelodysplastic syndrome and aplastic anemia, the use of artificial blood can improve their quality of life. In organ transplantation, artificial blood can be used to maintain donor organ survival and prevent or reduce reperfusion injury. People who reject blood transfusions because of religious and ethnic beliefs will also benefit from artificial blood in the future. The main side effects of blood transfusion are immunogenicity and infectivity. Therefore, a perfect artificial blood product must first be free of blood type restrictions and will not cross infection. While having the biological functions of normal human red blood cells to transport oxygen, it is preferable to have the advantages of ready-made products, long half-life and preservation at room temperature. In fact, the artificial blood that the researchers tried to invent is not really blood, nor does it play all the functions of blood, but a way to simulate the delivery of oxygen to various parts of the body. Therefore, artificial blood is also known as a blood substitute. The research and development of blood substitutes has been nearly 70 years old, but it is still a scientific problem that plagues academic, military and industrial circles. Past research has focused on mimicking the oxygen-carrying function of red blood cells. The blood substitutes that enter clinical trials are hemoglobin analogues, also known as hemoglobin-based oxygen carriers (HBOCs). Blood substitutes developed by Baxter, Borthfield, and Biopure have entered Phase 2 or Phase 3 clinical studies. The results show that although blood substitutes can exert the effect of delivering oxygen, they all have major side effects, including high blood pressure and unpredictable reduction of cardiac output. Overall, HBOCs have minimal effect on reducing blood transfusions after surgery and postoperatively, without reducing mortality and increasing the incidence of side effects. Based on current clinical trial results, the FDA has not approved the marketing of blood substitutes. At present, only one blood substitute Hemopure is approved by the South African government for clinical use, which is mainly due to the fact that South Africa is one of the regions with the highest incidence of AIDS, and there is a high risk of blood donation. Dr. Doctor's lab has found some innovative ideas for blood substitutes. He collaborated with Professor Dipanjan Pan of the University of Illinois at Urbana-Champaign (UIUC) to encapsulate hemoglobin into synthetic nanomaterials to avoid vasoconstriction and reduce the risk of heart disease and stroke. The blood substitute, called ErythroMer, has been shown in previous animal experiments to provide oxygen in response to the body's pH environment, transporting oxygen from the lungs to the body's most aerobic organs. Once the study is successful, ErythroMer can be stored as a lyophilized powder for several years and mixed with sterile water for use. In addition, the product also has the characteristics of immune silencing, and it does not cause an attack by the immune system when entering the human body, so it can be lost to any blood type. Although it sounds exciting, other industry scientists have conservative opinions about the artificial blood developed by Dr. Doctor. Dr. Ernest Moore, Vice President of the Center for Trauma and First Aid Research at the University of Colorado, mentioned that “(blood substitutes) is not as easy as it sounds†and he is also working on other blood substitutes. Mark Scott, a senior scientist at the Canadian Blood Center, said that “there is a lot of consideration in blood substitute research. For example, does the blood substitute particle size cause vascular leakage? Is the hemoglobin encapsulated in the outer shell stable? Acute or chronic poisoning?" In addition to overcoming many biological problems, Dr. Doctor will eventually convince the approving agencies that their products are safe enough for the human body (usually based on animal experiments). Based on the safety of previous blood substitutes, the FDA has approved a new clinical trial of blood substitutes at risk. Moreover, clinical trials related to trauma often lead to ethical issues of informed consent. It is foreseeable that clinical trials of artificial blood still have a long way to go. Dr. Doctor's research project has been funded by the Department of Defense. The data and results of experiments on small animals have also been published at the 58th annual meeting of the American Society of Hematology (ASH). Next, they need to further verify the safety and effectiveness of artificial blood products in large animal experiments, and study whether "will destroy other cells in the blood" and "whether to interfere with blood clotting" and other issues. If all goes well, it will take at least 8-10 years to enter the clinic. Dr. Doctor has set up a company called KaloCyte (Greek for “good cellsâ€) to develop the next step in artificial blood products. At present, the artificial blood used in the experiment is still synthesized by graduate students in small batches. 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