On January 14, 2022, Nature magazine published a news article "The first case of pig heart transplantation in humans, what can scientists learn?" It was reported that the team of the University of Maryland School of Medicine in the United States recently performed the world's first transgenic pig heart transplant on a male patient with advanced heart disease, and the operation was smooth, and the patient was able to get out of bed after surgery.
The patient who received a swine heart transplant was named David Bennett, and the team at the University of Maryland School of Medicine evaluated him as a patient with end-stage heart disease who had no other treatment options, and through a compassionate treatment program and received emergency authorization from the US FDA before New Year 2022, it can be said that animal heart transplantation is his last choice.
Animal organ transplantation to humans is called Xenotransplantation, so the researchers have genetically edited the pig heart, "knocked out" the three genes associated with organ rejection from the donor pig, and inserted 6 human genes received with the immune reception phase into the donor pig's genome, and also knocked out the pig gene that prevents the overgrowth of the pig heart, so far the pig heart has passed the ultra-acute rejection reaction, accelerated rejection reaction, acute rejection reaction, Later, the effects of chronic rejection should also be studied.
This news is very exciting for our doctors engaged in lung transplantation clinical and research work, and it has also caused us to think a lot, is it possible that one day in the future, pig lungs can also be transplanted to people? Just as our minds were racing, we were also celebrating big day for the lung transplant team – January 20, 2022.
On this day, the Department of Thoracic Surgery of Shanghai Pulmonary Hospital was extremely busy, and the lung transplant team will welcome three new patients, one is Lao Wang who was bypassed by ECMO before idiopathic pulmonary fibrosis (AE-IPF) surgery, one is Lao Gong who was transplanted 11 years after left lung transplantation and then performed contralateral transplantation, and one is Lao Zhu who has been transplanted twice with his right lung and transplanted for the third time.
Their stories
Lao Wang is 69 years old this year, 1 month ago the doctor suggested that Lao Wang do lung transplantation, when he did not make up his mind, always felt that he could still "hold on", after admission he always said "New Year's Day when I was still rubbing mahjong", he did not expect that the idiopathic lung fibrosis he suffered once the acute aggravation mortality rate will be very high, after admission to the hospital Lao Wang within 1 week of hypoxia progressive aggravation, high flow of oxygen has been unable to maintain, patients and families actively request lung transplantation, January 19 Shanghai Pulmonary Hospital Thoracic Surgery Lung Transplant Team immediately decided, Decided to start ECMO support: endotracheal intubation, ventilator assisted ventilation, femoral vein and intrajugular vein intubation, ECMO start, fresh blood flow after opening with body temperature into the ECMO pipeline, the patient's oxygen saturation rose sharply to 100%, heart rate, blood pressure is stable, and so on, it is already midnight, Li Yuping, deputy director of the Thoracic Surgery ICU, was relieved, considering that the patient's condition was unstable, so she continued to stay until dawn.
Lao Gong, 67 years old this year, 11 years ago in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital did allogeneic left lung transplant surgery, after the careful care of doctors and family, after the recovery is good, he works and lives like a normal person. 2 years ago Lao Gong rechecked the lung function appeared progressive decline, when the treatment considered the "chronic transplant lung rejection", although after drug adjustment treatment, Lao Gong still needs oxygen maintenance, the doctor recommended another transplant after evaluation, when he hesitated, 1 year ago, his wife experienced a serious illness and surgical treatment, and then he made up his mind to transplant again, Lao Gong said to us "I hope, in the future I can take care of her like she took care of me", so he firmly came to the thoracic surgery department of Shanghai Pulmonary Hospital again.
Old Zhu is 50 years old this year, when he was young, he was repeatedly tortured by "bronchiectasis", he traveled a long way to Shanghai in Inner Mongolia, 5 years ago in the thoracic surgery department of Shanghai Pulmonary Hospital did allogeneic right lung transplantation + left lower lung resection surgery, in 2020 because of the new crown epidemic, Lao Zhu failed to come to review in time, when re-admitted to the hospital, the right lung has been "all white", after excluding complications such as infection, considering "chronic transplant lung rejection", on November 2, 2020, he performed allogeneic right lung transplant surgery again, and the operation was very successful , with the first experience, quickly get out of bed active, recover very quickly. 3 months ago when the old Zhu re-examination again found that the lung function is progressively reduced, need to take oxygen again, and the symptoms of hypoxia are becoming more and more obvious, the lung transplant team after discussion suggested that the old Zhu consider the third transplant, in the face of greater surgical risks, the old Zhu and the whole family consulted, did not expect that the wife and son are very supportive of him, the old Zhu said "lung transplantation has allowed me to get two new lives, or many years later there is a better treatment than the lung transplant, I hope to live until that day", very lucky, old Zhu soon waited again for his lungs to be suitable.
Our transplant team
On January 20, 2022, the lung extraction team of Shanghai Pulmonary Hospital in Xiamen and Guangzhou began to obtain three donor lungs at 5:30, and all the lung extractions were well evaluated. At this time, the Shanghai sky is not yet fully bright, the cold wind is in place, the lung transplant team is all in place, Secretary Chen Chang, Director Jiang Guning, Director Zhu Yuming, Director He Wenxin, Director Chen Qiankun detailed inspection of the patient situation and the formulation of personalized surgical plans, Director Su Yiliang, Director Li Yuping from 6:30 onwards to transport three critically ill patients, including a patient with tracheal intubation and ECMO transport. Three operating rooms, before the delivery of the lungs, successfully completed the separation of the patient's sick lungs, for the lung to arrive after the transplant team immediately divided the work, the surgical group physician quickly removed the separated residual lung, while the lung repair group physicians on the supply lung to trim, in the monitor rhythmic heartbeat sound, the transplantation work is carried out in a tense and orderly manner. According to the original plan, Lao Wang successfully did a double lung transplant, Lao Gong did a sequential transplant of the right lung, and Lao Zhu did a third transplant of the right lung, and the postoperative vital signs were stable. Lao Gong removed the tracheal tube on the first day after the operation and went out of bed the next day; Lao Wang and Lao Zhu also removed ECMO on the second and third days after the operation.
In the exhaustion of a day of high-intensity surgery, we fell into new thinking, although we completed three lung transplants in one day, but looking at the long waiting list of lung transplant patients, thinking of faces that are anxiously waiting for breathing difficulties, we hope that donor lungs can come more and earlier, so that we can perform lung transplants earlier for these terminal lung patients, knowing that these patients face the threat of death at any time. However, at present, the number of lung transplant donor donations in mainland China and the success rate of donor lung maintenance are far from enough, and a considerable number of patients with end-stage lung disease have unfortunately died while waiting for transplantation.
The American Journal of Organ Transplantation (AJT) recently reported that a team at the University of Alabama in Birmingham performed bilateral renal resection of a brain-dead double kidney donor and subsequently transplanted two kidneys from a genetically modified pig into the deceased. The deceased remained hemodynamically stable by reperfusion, although the pig kidneys were exposed to human blood pressure, the integrity of the blood vessels was maintained, no hyperacute rejection was observed, the pig kidneys remained alive within a 74-hour observation period, no chimera or transmission of the pig retrovirus was detected, pathological biopsy had only mild microvascular thrombosis, the pig kidneys could produce considerable urine output, but the creatinine clearance capacity was not restored.
Judging from these bold attempts, it seems that pig hearts and pig kidneys are likely to be used in clinical transplantation in the future, is it possible to transplant xenopulmonary transplantation?
As early as 1998, Miyata and others used hamsters as lung transplant donors, rats as lung transplant recipients, post-transplant recipient survival time of more than 3 months, the success of xenopulmonary transplantation of small animals made the academic community very excited, and then many scholars did xenopulmonary transplantation of large animals, but the survival time was very short. At present, many scholars are studying the possibility of transplanting pig lung of donors with different gene edits into baboons, but the survival time is still very short. The results of the xenopulmonary transplant study are frustrating because the lungs have some unique immune and non-immune barriers (such as baboons have antibodies that humans do not have, which attack proteins on pig organs), and these barriers hinder the progression of xenopulmonary transplantation. In order for xenopulmonary transplantation to be possible, more innovative research must be done in donor gene editing, coagulation disorders and new therapies that induce tolerance, and perhaps with the joint efforts of everyone, xenopulmonary transplantation will become a new clinical possibility at some point in the future, so that the lung transplant team in our hospital can bring hope to more patients with end-stage lung disease.
The Department of Thoracic Surgery of Shanghai Pulmonary Hospital began to carry out lung transplant animal tests led by Professor Ding Jia'an as early as the 1970s, and officially carried out clinical lung transplantation in 2003, under the leadership of Professor Jiang Gening, Professor Chen Chang, Professor Zhu Yuming, etc., after more than ten years of unremitting efforts, thick accumulation and thin hair, shanghai Pulmonary Hospital has achieved a lung transplant team with excellent technology and tacit cooperation. In recent years, lung transplantation work has developed vigorously and rapidly, and a total of 41 high-quality lung transplants have been completed in 2021, including preoperative ECMO bridged critical lung transplantation, the first case of COPD combined lung cancer in China after 9 years of total lung resection on one side and then contralateral lung transplantation, etc. At the beginning of the new year in 2022, 5 lung transplant surgeries of various types have been completed, and the lung transplant team completed 3 high-difficulty lung transplants in a single day, which shows the thickness and depth of our team's technical strength.