[2023 "Science Popularization China Youth Star Creation Competition"] New Heart · Confidence

The winning works of the 2023 "China Science Popularization Star Creation Competition" are: Xiang Xin, Lin Yuhan, Guan Xin, Chen Yijia, Long Huan, Zeng Yongwei, Zhang Caini

When patients need to undergo heart transplant surgery, their heart function is often very poor, and most of the time, there is a problem with the patient's own myocardium. The heart is like the engine of the human body. When the engine has a minor problem, we can use oil or a small repair to keep the engine working. However, when the engine is seriously damaged and can no longer be repaired and may stall at any time, we can only replace the engine. The same is true for heart transplantation. When heart disease is so serious that it cannot be treated with drugs and general surgery, the only solution is a heart transplant.

The earliest description of organ transplantation can be traced back to the myths of ancient Greece, Rome, China and India, which mentioned bone, skin, tooth, limb and heart transplantation. Since the 16th century, many medical experts from different countries and fields have been trying to perform organ transplantation operations. It was these predecessors' experience that laid the foundation for South African heart surgeon Barnard to successfully complete the first heart transplant in human history in 1967. Although the patient only survived for 18 days after the operation, it opened the door to heart transplantation for mankind. According to statistics, nearly 6,000 heart transplants are completed each year in the world. In 2019, my country completed 658 heart transplants. The success rate of heart transplantation in my country exceeds 95%, and the in-hospital survival rate has exceeded 90%. my country's heart transplantation has made great progress in both quantity and quality.

Heart from a medical perspective. Image from the Internet

The most obvious feeling of patients after heart transplantation is the significant improvement of symptoms and the greatly improved quality of life. However, since anti-rejection drugs will inevitably suppress the patient's immune system, patients need to maintain hygiene as much as possible in their daily lives, wash their hands frequently and disinfect frequently to minimize the risk of infection. In addition, they also need to maintain a healthy lifestyle after surgery, control blood pressure, blood sugar and blood lipids, have a regular work and rest schedule, eat a reasonable diet, take medicine on time, and reduce the burden on the heart as much as possible.

Of course, there are also inevitable difficulties in heart transplantation. Although the number of organ donations after the death of Chinese citizens has increased year by year, and is currently ranked first in Asia and second in the world, the source of heart donors is still huge, and the supply of heart donors is in short supply, which is also one of the problems currently facing heart transplantation. In addition, the body's rejection reaction after heart transplantation is inevitable. After all, it is not a native heart and it is impossible to adapt to the body like the original heart. There will be more or less rejection reactions. If the rejection reaction is very severe, the inflammation will damage other organs, and the patient must take anti-rejection drugs for a long time, and the subsequent costs may be unaffordable for some families.

Knowing what heart transplantation is, it is not difficult to understand xenotransplantation. This method is to transplant the heart of one species into another species. Compared with homologous transplantation, xenotransplantation seems to solve the problem of organ shortage, but the differences between different species are greater and the rejection reaction is stronger. Therefore, it is crucial to choose the source of the transplant.

The first thing that comes to people’s mind is the primates that are most closely related to us, such as chimpanzees, monkeys, etc. However, primates are not the best choice for xenotransplantation due to their scarcity, difficulty in breeding, high price, small organ size, and possible ethical debates. Since the “big brother” cannot be relied on, we have to sacrifice our “second brother” Zhu Bajie. Although pigs and humans look very different, the structure and size of pig hearts are roughly similar to those of humans. The evolutionary distance between pigs and humans is just right, and the viruses in pig tissues are unlikely to cause human infection. In addition, pigs are easy to breed and reproduce on a large scale. Various factors have made scientists have a special liking for pigs. So far, it has become an international consensus that pigs are the best choice for xenotransplantation.

On January 7, 2022, David Bennett, a 57-year-old patient with advanced heart disease, received a pig heart transplant. He was also the first patient in history to receive a pig heart transplant. This donor pig was not simple at all. There were 10 gene modifications in its genome. In addition, the treatment team also used an experimental anti-rejection drug. Unfortunately, this epoch-making operation came to a temporary end with Bennett's death two months later.

Since the idea of ​​using xenotransplantation, scientists have faced two difficulties: how to overcome rejection? How to keep the organ size suitable for humans? With the development of science and technology, scientists have found some answers using gene editing technology: they knocked out three pig genes that would quickly cause organ rejection and a gene that regulates growth, and added six human genome genes to enhance the pig heart's tolerance to the human immune system.

Gene editing seems to be a powerful tool that can do anything. But can it really solve all problems? In fact, the reality is much more complicated.

Take growth hormone for example. In addition to regulating growth, growth hormone also has an important impact on the maintenance of normal morphology and function of the human heart, not to mention if a child needs a transplant, is there any way to make the pig heart grow only to the size we need? The emergence of mini pigs has given us hope.

In addition, viral infection remains a deep concern in pig heart transplants. Although researchers are committed to finding genetic engineering methods to create pigs that do not transmit retroviruses, this field still faces huge challenges. Viral infection has become one of the main reasons for failure of xenotransplantation, which means that we still have a long way to go and more in-depth research and development are needed to completely solve this problem. Although technologies such as gene editing have brought us some hope, further research and development are still needed to achieve successful xenotransplantation. We must focus on solving the problem of viral infection to ensure that xenotransplantation can become a safer and more effective treatment option in the future.

Doctors at the University of Maryland School of Medicine are performing a pig heart transplant. Image from the Internet

However, waiting for a suitable transplant heart is a long process. In addition to meeting the requirements of size and blood type, it is also necessary to prevent infection of the donor. So, in addition to allogeneic hearts, are there any other ways to alleviate the shortage of donors? The advent of 3D printing technology provides some ideas for answering this question.

In 2019, researchers at Tel Aviv University in Israel created the world's first 3D-printed heart with cells and blood vessels. The researchers first collected fat tissue from the patient, then separated the cells and non-cellular substances in it. The separated cells were then differentiated into myoblasts and cells that can generate blood vessels, and then mixed with special printing materials to make "bio-ink" that is suitable for 3D printing, and finally printed out heart tissue suitable for the patient. Since 3D printed heart transplants can create artificial hearts that match the patient's own heart, it can improve the success rate and survival rate of heart transplant surgery. It can also avoid problems such as donor heart shortages and rejection reactions, thereby improving the patient's survival and recovery quality.

Compared with other traditional transplantation technologies, 3D printing can not only be customized at any time, so that patients on the verge of death no longer have to wait for the "fatal part", but also because the materials required for 3D printing come from the patient's own tissues and cells, it prevents immune rejection caused by homologous transplantation and heterologous transplantation. Of course, there are still areas worth exploring in the current 3D printing heart technology, including how to expand cells to make them compatible with the human heart. I believe that in future research, 3D heart printing technology can be used clinically.

3D printed heart Image from the Internet

Heart transplantation is an urgent matter for patients who need a new heart. With the continuous development of science and technology, new technologies and new solutions emerge in an endless stream. Heart transplantation has also evolved from the original homologous transplantation to xenotransplantation, and then to 3D printed heart transplantation. New technologies bring hope to patients. I believe that in the future, more technologies that benefit patients will gradually come out. By then, technology will break through the barriers of donor restrictions, so that every patient can fairly enjoy the right to "new heart transplantation"!