What is the difficulty of transplanting animal organs into the human body?

Ongoing transplant surgery. Image source: Massachusetts General Hospital's official website

Science and Technology Daily reporter Zhang Jiaxin

Recently, the Massachusetts General Hospital in the United States announced that the world's first living patient who received a genetically modified pig kidney transplant died 50 days after surgery.

"Mr. Sleman will always be seen as a beacon of hope for countless transplant patients around the world," the hospital said in a statement. We are deeply grateful for the trust he has placed in him and his willingness to advance the field of xenotransplantation. ”

Xenotransplantation is the transplantation of living cells, tissues, or organs from one species to another in response to a shortage of human organ supplies. Pigs are one of the best donors for xenotransplantation because of their organ structure, physiological function and size, which are similar to human organs. However, there are still many difficulties and risks in this field, and a reporter from Science and Technology Daily interviewed Chen Gang, deputy director of the Organ Transplantation Institute of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.

The surgery was a milestone

According to the Washington Post, in addition to kidney disease, Sleman also suffers from high blood pressure and type 2 diabetes. The transplanted kidney he received was taken from gene-edited pigs provided by eGenesis in the United States. The pig underwent 69 gene editing, knocking out 3 important xenoantigen-related genes and adding 7 human transgenes to improve compatibility. At the same time, eGenesis also inactivated viruses that are inherent in pigs and have the potential to infect humans.

The Massachusetts General Hospital statement noted that there was no indication that the patient's death was the result of a recent transplant. The exact cause of death has not yet been announced.

However, Chen Gang revealed in an interview with reporters that he learned from the American research team the day after Sleman's death that the patient died of a sudden heart attack.

Chen Gang believes that although the results are regrettable, this operation is still a milestone in the field of xenotransplantation. It demonstrates the technical feasibility of xenograft and provides valuable data and experience for future research.

There are many technical difficulties in xenotransplantation

Organ shortages have long plagued the world. Massachusetts General Hospital revealed in March that it had more than 1,400 patients on its waiting list for kidney transplants. Medical experts at the hospital expressed hope that the transplant would bring hope to millions of patients with kidney failure around the world. However, xenotransplantation still faces many challenges before it can be truly applied in clinical practice.

Chen Gang gave an in-depth analysis of the challenges faced by xenotransplantation.

First of all, the choice of clinical indication is the first difficulty in xenotransplantation. This is a complex process, and doctors need to consider a variety of factors such as the patient's physical condition, age, and medical history when deciding to proceed with a transplant.

The second is the diagnosis and treatment of xenotransplant rejection. According to the New York Times, Sleman showed signs of cellular rejection, the most common form of acute graft rejection, on the eighth day after surgery. Up to 25% of organ recipients experience cellular rejection within the first 3 months.

"Although the treatment of acute rejection of allotransplantation is well-established and effective, in xenotransplantation, once rejection occurs, even cellular rejection, it is difficult to reverse and may lead to serious consequences. Current treatment options still lack technical support, and increasing drug dosage or intensifying measures to prevent rejection may lead to serious complications. Chen Gang said.

In addition, xenotransplantation has functional problems. For example, pig kidneys produce an alarming amount of urine, which not only requires patients to drink a lot of water, but also tends to cause dehydration. Patients after pig kidney transplantation may be prone to acid-base imbalances or electrolyte abnormalities, which require regular monitoring and timely adjustment. In addition, erythropoietin produced by pig kidneys is only suitable for pig bodies, and patients need to regularly supplement human erythropoietin to avoid anemia. For pig heart transplantation, whether it can meet the needs of human mobility and exercise is also yet to be studied.

The drug problem is also a problem that needs to be solved urgently. Antibodies that block the CD154 and CD40 molecular pathways have been found to be important for long-term survival in xenotransplantation, but these antibodies are still experimental and the long-term risks are unknown.

Post-transplant complications are another important aspect of xenotransplant surgery. Because immunosuppressive measures may be stronger than homogeneous transplantation, and the impact on the body's immune system is also greater, it is easy to lead to the destruction of the innate immune system and the development of infectious complications.

Biosecurity and ethical risks coexist

Chen Gang introduced that in xenotransplantation, cross-species biosecurity and ethical issues have also been of great concern. It is generally accepted that the closer a species is to humans, the more likely it is to infect humans with pathogens. Among xenografts using porcine organs, porcine endogenous retrovirus (PERV) is the most difficult to eliminate, followed by porcine cytomegalovirus (PCMV). The transplanted pig kidney that Sleman received was knocked out of the gene associated with PERV.

In the world's first autopsy of a pig heart transplant patient, scientists found signs of PCMV, which may have contributed to the patient's subsequent heart failure and death.

Chen Gang added that it is also necessary to pay attention to whether the pig's genes will "contaminate" the human genes after organ transplantation. The transplanted organ will participate in the body's circulation and interact with the body at the cellular level, and may even cause gene mosaicism, which may lead to potential genetic risks.

Despite the many challenges, the human exploration of xenotransplantation has not stopped. On April 12, New York University Langone announced the successful completion of the world's second living donor pig kidney transplant. Chen Gang revealed to reporters that the patient has not reported any abnormalities so far. This surgery is the first operation in human history to transplant an artificial mechanical heart and a pig kidney with porcine thymus tissue, bringing new hope and impetus to the field of xenotransplantation.

Looking ahead, Chen Gang said that with the in-depth development of gene editing technology and immunology, xenotransplantation is expected to become a supplement to allotransplantation to fill the huge gap in organ supply and bring hope to more patients. However, in this process, various technical and ethical challenges need to be carefully addressed to ensure the safety and efficacy of xenotransplantation.

(Source: Science and Technology Daily)

For more exciting information, please download the "Jimu News" client in the application market, please do not reprint without authorization, welcome to provide news clues, and pay the remuneration once adopted. 24-hour hotline: [phone].