After five years of research, the research team successfully put on a special' coat' for red blood cells, so that blood donors and recipients can carry out blood transfusion even if their blood types are different, and the artificial construction and safe blood transfusion of' universal panda blood' have been realized.
If this technology can be successfully applied in clinical practice, the current situation of insufficient blood reserve of special blood types will become history, and rare patients with panda blood will no longer fall into crisis because blood is hard to find.
What blood type is it? Who is in charge?
When it comes to blood type, ABO blood group system may be the first thing people think of. ABO blood group system is the most common and important, but not the only one. In addition to ABO, there are blood group systems such as Rh.
What determines the blood type?
The essence of blood type is actually the antigen type carried on the surface of red blood cells in human blood. The antigens in ABO blood group system are A, B and H, and their essence is the sugar chain connected between lipid and protein. Human red blood cells with type O blood carry H antigen. People with type A blood also carry H antigen, but the A gene they carry can convert H antigen into A antigen. Similarly, people with type B blood can modify H antigen into B antigen with B gene. Type AB people carry both gene A and gene B, which can modify H antigen on the surface of red blood cells into antigen A or antigen B. 。
Rh blood group system is independent of ABO blood group, and its antigen is protein on the surface of red blood cells, including C, C, D, E, E and so on. Among them, D antigen is the most important one. People with D antigen are called Rh positive, and those without D antigen are called Rh negative.
Rh blood group is as important as ABO blood group, but compared with ABO blood group, many people don't know about Rh blood group. This is because in China, more than 99% people have D antigen, so it is almost unnecessary to consider the consistency of Rh blood group system when matching blood transfusion.
But there are also people with 1% Rh negative blood group. Because of their rarity, they are often much more dangerous than ordinary people when blood transfusion is needed. Because it is difficult to have enough blood reserves suitable for them in the blood bank, Rh negative blood group is also called' panda blood'.
Because the blood type is rare and Rh is negative, people set up mutual aid organizations all over the country: these people with the same rare blood get together to form a' blood-activating bank', which adds a guarantee for each other's safety.
Why do blood transfusions need matching?
Blood types are called "antigens" because they can cause the body's immune response. If a person enters an antigen that he didn't have before, the immune system will attack these pagans to ensure the purity of the internal environment. In the process of blood transfusion, if a person who has been transfused with type O blood is transfused with type A or type B blood, his/her immune system will attack an unprecedented type A or type B antigen. This immune attack will lead to adverse blood transfusion reactions such as red blood cell rupture, which will be life-threatening in severe cases.
Rh-negative people also lose Rh-positive blood. Therefore, for people who are Rh-negative, especially those who are O-Rh-negative, it is a crucial event to mix other antigens during blood transfusion.
Universal panda blood', blood transfusion does not need matching, how is it done?
As mentioned above, the surface of red blood cells in Rh-positive blood carries D antigen. The first entry of D antigen into Rh-negative people will not cause danger, but it will induce Rh-negative people to produce antibodies that can bind to D antigen. If D antigen enters this human body for the second time, these antibodies will react strongly with D antigen, which is life-threatening. Therefore, in an emergency, Rh-positive blood can be given to Rh-negative recipients, but only for the first time, and there will be obvious immune response the second time.
How to make the immune system of Rh-negative recipients ignore D antigen? One way is to hide the D antigen. This "universal panda blood" researcher
The research team wrapped Rh-positive red blood cells with a three-dimensional gel network similar to the outer layer of cell membrane, which is equivalent to putting a coat on red blood cells, so that the D antigen carried by red blood cells is hidden in the three-dimensional gel network, so that it will not be recognized by the immune system, thus naturally causing no immune response.
Having said that, some people may have doubts: can the red blood cells in a' coat' still play a role?
Because the' coat' is soft and breathable, it will not affect the elasticity of red blood cells, and it can also ensure the normal passage of oxygen and carbon dioxide. The red blood cells of mice wearing coats have the same function in vitro as unmodified red blood cells, and have similar distribution and life span in vivo.
The researchers also tested the immunogenicity of human red blood cells in rabbits wearing' coats', and the experimental results proved that this' coat' can effectively shield D antigen. In addition, the researchers also predict that this' coat' can also shield A and B antigens in ABO blood group system, making the transformed red blood cells become universal O type.
Of course, this study is far from clinical application, and there are still some problems to be solved at this stage.
First of all, although the reconstructed red blood cells look normal in vitro, can they maintain normal function in the internal environment? Secondly, will these modified red blood cells have side effects when metabolized in the body? Thirdly, from the experimental data, although rabbits only received a small amount of modified red blood cells, they still had a small amount of antibodies. So, when the modified red blood cells are used in a large number of people, is it still safe?
The real O-Rh negative red blood cell reconstruction project is the holy grail of blood transfusion. If the above problems can be solved, this research will be a milestone in the history of human blood transfusion.
In addition to being overwritten, you can also modify the blood type.
Rh antigen is a kind of protein, which can't be modified, but can only be masked, while the anti-ABH principle is a kind of sugar, which is relatively easy to be transformed into each other. As mentioned above, genes A and B can change H antigen into A and B antigens, and in this process, a carbohydrate molecule needs to be added to H antigen.
In order to make universal O-type red blood cells, scientists have been looking for enzymes that can reduce A and B antigens to H antigens in vitro. In fact, the enzymes that can reduce A antigen and B antigen to H antigen were discovered in 2007 and 1982 respectively, and they are constantly being updated. However, due to the problems of conversion efficiency and cost, this technology has not been applied to clinic.
In order to solve the problem of blood use, scientists are also considering artificial production of simulated blood, trying to develop a universal, easy-to-preserve and easy-to-use red blood cell substitute to achieve the purpose of blood transfusion.
The main purpose of blood transfusion is to restore the oxygen/carbon dioxide transfer ability of patients with blood loss. It is a method to modify red blood cells obtained from human body in vitro. At the same time, people have been exploring other substances that can carry oxygen and carbon dioxide besides red blood cells, among which hemoglobin oxygen carrier and perfluorocarbon oxygen carrier are the most important two.
Hemoglobin is the main functional component of red blood cells and is responsible for carrying oxygen molecules. However, hemoglobin leaving red blood cells has too strong binding force with oxygen, which will combine with nitric oxide in blood vessels and cause vasoconstriction. Because of these defects, hemoglobin cannot be directly used for blood transfusion. In order to modify hemoglobin, people try to make hemoglobin-based oxygen carriers by gene recombination, crosslinking, polymerization and encapsulation.
An American invention uses synthetic nano-materials to wrap hemoglobin to make small artificial red blood cells, and then makes them into freeze-dried powder for long-term storage. When it needs to be used, it can be quickly put into use by adding water to dissolve it. Although the average residence time of this artificial red blood cell in the body is only 8 to 12 hours, it can also play an important role in first aid.
The compound perfluorocarbon is not only used directly in hemoglobin of organisms, but also used in artificial blood, because it can bind and release oxygen. Perfluorinated carbon is insoluble in water, so it needs to be made into emulsion and mixed with antibiotics, vitamins, nutrients and salts to form artificial blood.
Artificial blood prepared from perfluorocarbon has been used in clinic, but it has not been widely popularized and used because it is not easy to store and patients need to inhale high concentration oxygen to maintain its function.
Although the research of artificial blood has made great progress, there are still great challenges. In the future, clinical medicine will still rely on loving blood donation to ensure normal blood supply.
Processing human red blood cells to make them more' universal' is an important means to make up for the shortage of technology and manpower. If the' universal panda blood' technology developed by Zhejiang University team can be successfully applied to clinic, it will be the first technology in the world that can produce Rh-negative blood in large quantities, which is undoubtedly good news for people with Rh-negative blood types.