Organ transplant experts from the World Health Organization, the United States and Germany recently gathered at the First Affiliated Hospital of Sun Yat-sen University in Guangzhou. The purpose of their visit was to observe a liver transplant operation using original Chinese technology.

This operation used the cutting-edge technology of Professor He Xiaoshun's team at the First Affiliated Hospital of Sun Yat-sen University - the non-ischemic organ transplantation technology. This technology solves the problem of ischemic damage to donor organs in organ transplantation surgery and enables donor organs to be transplanted in the "freshest" state. In recent years, it has attracted widespread attention from the global organ transplantation industry.

"This technology will have a significant impact on organ transplantation in China and the world." said John Fung, the incoming president of the Transplantation Society (TTS).

This is a microcosm of the global attention paid to the new track of "organ medicine" pioneered by Chinese scholars. In 2017, He Xiaoshun's team successfully broke through the key technology of "ex vivo organ maintenance" and pioneered the "non-ischemic" organ transplantation technology. In 2019, they took the lead in proposing the concept of "organ medicine" internationally, pushing China to a leading position in the world in the field of organ-level research and treatment of diseases.

From the "milestone" of organ transplantation to the "new track" of organ medicine

As the second largest country in the world in terms of organ donation and transplantation, China's breakthrough in organ medicine technology was originally aimed at solving problems such as poor prognosis caused by organ ischemia damage in organ transplantation.

In 2017, He Xiaoshun, then vice president of Zhongshan First Hospital and leader of the organ transplantation discipline, led his team to complete the world's first non-ischemic liver transplantation in Guangzhou using the independently developed "ex vivo multi-organ maintenance system", which caused a sensation in the international organ transplantation community.

Modern organ transplantation technology was invented by American doctor and Nobel Prize winner Joseph Murray in 1954 and has been used ever since. After the donor organ is removed, it must be placed in ice for "cold storage", which damages the organ quality and affects the transplantation effect. The new technology ensures that the blood supply to the organ is not interrupted during the whole transplantation process and the organ maintains normal physiological function, realizing the technical iteration of organ transplantation from "cold transplantation" to "hot transplantation".

Clinical research results show that this technology greatly reduces the incidence of complications related to ischemic injury after liver transplantation, and the long-term survival rate of patients has been significantly improved. The American Journal of Organ Transplantation published an article stating that the ischemic organ transplantation technology is a milestone in the history of organ transplantation, and organ transplantation will enter the era of "hot transplantation".

Since then, He Xiaoshun's team has successfully carried out the world's first ischemic kidney transplant and ischemic, beating heart transplant in 2018 and 2021. Compared with traditional transplantation, the incidence of complications of new transplantation technology has been significantly reduced, and the utilization rate of organs has been greatly improved.

In the world's first ischemic heart transplantation in June 2021, a 67-year-old male patient with dilated cardiomyopathy successfully received a heart that remained "fresh" from acquisition, preservation to implantation. During the operation, which lasted more than 4 hours, the donor heart achieved uninterrupted blood flow and a "beating" heart with the support of an in vitro multi-organ maintenance system.

"Non-ischemic heart transplantation technology can protect the donor's heart function to the greatest extent, prolong the in vitro preservation time, improve the transplantation efficacy, and allow patients to survive longer and have a higher quality of life." He Xiaoshun said.

Based on the continuous breakthroughs in a variety of ex vivo organ maintenance technologies, He Xiaoshun's team was the first in the world to propose the concept of "organ medicine" in 2019, and successfully opened up a new medical track for studying and treating diseases at the organ level. It has now become a major frontier focus in the global medical community, with broad research and application prospects, and its disruptive impact on medical clinical practice, teaching and scientific research has also begun to emerge.

Promoting medical standards to new heights

At the "2023 China Life Science Conference" held in May last year, Huang Jiefu, chairman of the Chinese Human Organ Donation and Transplantation Committee, said that although Western medicine originated in Europe and the United States, the concepts and technologies of organ medicine created by Chinese scientists are expected to open up a new track for the development of medicine.

Huang Jiefu said that in the future, Chinese scientists are expected to achieve a series of original major breakthroughs and product transformation in the fields of organ transplantation, organ research, organ teaching, organ drug screening, organ treatment, organ replacement, etc.

In terms of organ transplantation, the problem of organ donation shortage can be effectively alleviated. The shortage of transplanted organs is a global problem. At present, brain-dead organ donations are the main source of transplanted organs, but more than 99% of clinical deaths are cardiac deaths. At this time, all organs in the body are difficult to use for transplantation due to long-term ischemic damage.

He Xiaoshun said that by using the "organ rescuer" technology developed by his team, it is possible to save organs such as the liver and kidneys and ensure their stable blood supply after the deceased's heart stops beating and clinical death is declared. This can not only win precious time for organ donations, but even allow some "marginal organs" with poor indicators to be used, thereby improving organ utilization.

"There are not enough organ donations in the world at present, which leads to restrictions on transplantation." Efstratios Chatzixiros, a consultant on organ, tissue and cell transplantation of the World Health Organization who came to Guangzhou to observe the operation of He Xiaoshun's team, said, "We have seen that innovative surgical techniques have increased the possibility of organ utilization, especially for organs that are considered to be in poor condition or even rejected under the cold preservation technology system. Now, the potential of donated organs can be maximized."

In terms of organ treatment, "headache treatment, foot pain treatment" precision treatment is achieved. Based on organ medical technology, it has become a reality to protect and treat diseased organs separately. At present, the first kidney isolation protection treatment and the first liver cancer targeted treatment have been successfully implemented one after another.

In October 2023, He Xiaoshun's team cooperated with the expert team of the Seventh Affiliated Hospital of Sun Yat-sen University to complete an innovative liver cancer targeted chemotherapy using "organ targeted treatment" technology. With the support of the organ maintenance system, the operation achieved high-concentration chemotherapy drugs only acting on the cancerous part of the patient's liver, while the healthy part of the liver and the whole body were not affected, achieving a new breakthrough in the field of precision treatment of liver cancer.

Tang Di, deputy chief physician of general surgery at Zhongshan No. 7 Hospital, said that previous tumor chemotherapy was "systemic chemotherapy", that is, if one organ was sick, all organs were treated; while organ-directed therapy technology has achieved "only treating the organ that is sick", and the relevant patients did not experience common chemotherapy side effects such as nausea, vomiting, and hair loss, which is expected to provide a new strategy for tumor chemotherapy. After treatment, the advanced patient has been tumor-free and survived to this day. "We isolate the blood supply of the target organ from the human body and only use local high-concentration drugs to maximize the efficacy and minimize side effects." He Xiaoshun said.

In terms of organ replacement, organs can be temporarily "hanged on" to save lives. Organ medicine technology can not only achieve organ transplantation without ischemia throughout the process, but also allow the patient's diseased liver to recuperate by "hanging on" the liver, thereby providing new ideas for the clinical treatment of patients with acute liver failure.

It is reported that when a patient's liver fails acutely, a healthy liver can be temporarily "hanged on" for replacement therapy. After the patient passes the critical period and his own liver function is restored, the external liver support will be withdrawn. This is expected to change the fate of patients with acute liver failure who must undergo organ transplantation. At present, the large animal test of this technology has been successful.

The transformation of new quality productivity of 100 billion yuan is accelerated

Many medical experts interviewed said that most of the global Western medicine research, from populations, individuals, cells, and molecules, has been developed by the global medical community at different levels. Only "organ medicine" between individuals and cells and in the meso-dimensional dimension has great potential and broad application prospects. Now China is expected to achieve "lane change and overtaking" in this field and lead the development of modern medicine.

At the same time, according to estimates by relevant research teams, as a new quality productivity with huge potential, "organ medicine" is expected to drive the formation of an emerging industry of 100 billion yuan.

In terms of organ teaching, living animal organs can be "turned from waste into treasure" for teaching. At present, the world's first "living organ" surgical training system has been successfully developed and widely used. It can use animal organs such as pig viscera to provide surgeons with the opportunity to "practice" laparoscopic and endoscopic surgery.

There is a saying that surgeons grow up according to the "10,000-hour rule", that is, they need to do 10,000 hours of surgery to become experts. However, after entering the era of minimally invasive surgery, the operation is generally performed by the surgeon under the laparoscope. It is difficult for young doctors to have the opportunity to "get started", and most of them can only practice with plastic teaching aids.

Zhao Qiang, chief physician of the Organ Transplant Center of the First Hospital of Zhongshan University and deputy director of the Horizontal Department of the Institute of Science of Zhongshan University, introduced that the system can keep animal organs from slaughterhouses alive, changing the current way that medical students generally conduct surgical training on plastic models or practice on computer virtual teaching machines, creating a real surgical environment, greatly shortening the surgical training process, and establishing surgical evaluation standards. The system has been applied in many colleges and hospitals such as Zhongshan University, Wuhan University, and Capital Medical University, and achieved good results.

Industry insiders analyzed that the market size of organ teaching driven by the "living organ" surgical training system is conservatively estimated to reach 4.2 billion per year in China, and more than 26 billion per year internationally.

In terms of organ drug screening, in vitro "living organ" drug testing will be achieved to shorten the research and development time. The team used the developed equipment to cultivate the diseased organs removed by surgery in vitro to test the effect of new drugs on the organ, thereby simplifying the time and cost of clinical trials and avoiding the repeated trial and error of new drug development from cell screening, animal experiments to clinical trials, which is expected to reduce the research and development time and economic costs by more than 70%.

"For example, after the liver is kept alive in vitro, we can accurately evaluate which substances it synthesizes and which substances it metabolizes." Zhao Qiang said that now researchers can cultivate the liver alone in vitro to study and understand the function of the organ, and at the same time use it to test the effect of new drugs on the organ, which opens a new window for drug clinical trials.

At present, He Xiaoshun's team is building an organ model of human disease, aiming to solve the problem of "unreality" of existing medical research models, and become a powerful tool for studying diseases and developing new drugs.

According to industry insiders, the international drug development market is worth 401.9 billion yuan, and the tumor marker market is worth 105.6 billion yuan. Organ drug screening technology is expected to reconstruct the theoretical and technical system of new drug evaluation, accelerate the process of innovative drug development in China, and promote the transformation of the international drug development market and tumor marker market.

The transformation of the cutting-edge industry of organ medicine continues to advance. He Xiaoshun said that the "non-ischemic liver perfusion system" independently developed by his team has recently passed the approval of the Medical Device Technology Review Center of the State Food and Drug Administration at one time, and officially entered the "green channel" of the special review procedure for innovative medical devices and carried out clinical trials; the National Health Commission has also launched a multi-center normothermic mechanical perfusion clinical study in many hospitals in China.

"We will further accelerate the construction of China's original organ medicine platform, speed up the research and development and application promotion of organ medicine-related equipment, improve the current disease diagnosis and treatment efficiency, innovate the medical model, meet the people's growing health needs, and continue to lead the development of organ medicine." He Xiaoshun said.

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