World's first! Gene-edited pig heart transplanted into human body

The University of Maryland School of Medicine issued a statement on the 10th saying that medical experts transplanted a genetically modified pig heart into an American heart patient, which is the first case in the world. This is the world's first transgenic xenotransplantation of the heart. The patient is currently in good condition, but is still under observation. Doctors will evaluate whether the transplant was successful in a few weeks.

Human rejection is usually a problem in xenotransplantation. Why did this pig heart transplantation surgery achieve such great progress? What technological breakthroughs were involved?

The patient who received the transplant is on the right, and the surgeon on the left (Image source: University of Maryland Medical Center)

On January 7, doctors at the University of Maryland School of Medicine transplanted a gene-edited pig heart into a patient for the first time. Image source: https://phys.org/

How to transplant a pig heart into a human?

The man's name is David Bennett. He suffers from heart failure and has entered the terminal stage. He cannot maintain normal heart and lung function without the help of machines. The day before the operation, Bennett said: "It's either death or a pig heart transplant. I want to live. I know this is a last resort, but this is my last choice."

Judging from the postoperative situation, the gene-edited pig heart transplant did not cause an immediate rejection reaction in the human body. The next few weeks are still very critical, and doctors will closely monitor the activity of the transplanted heart. If the gene-edited pig heart can work normally in the human body, this operation may become a milestone.

Many pig organs are highly similar to human organs, but there is a huge obstacle to xenotransplantation: the human immune system may reject foreign tissues or organs, even with fatal consequences.

The main reason why scientists want to genetically modify pigs is to suppress these rejection reactions and prevent the patient's immune system from attacking the pig's heart.

Last October, a team led by Dr. Robert Montgomery at NYU Langone Health successfully transplanted a gene-edited pig kidney into a brain-dead patient with renal dysfunction—her family agreed to the experiment just before she was about to be taken off life support. The pig kidney reportedly began to produce urine and excrete waste creatinine "almost immediately," a sign of good kidney function. The initial experiment was terminated after 54 hours, during which time the kidney showed no macroscopic properties associated with rejection.

Although xenotransplantation technology has not yet been approved for use, the U.S. Food and Drug Administration (FDA) has a "compassionate use" clause that applies when a patient faces a serious or life-threatening medical condition and only has an experimental treatment as an option. Bennett received special permission from the FDA on New Year's Eve, which gave him the opportunity to receive the transplant.

The operation is in progress. Image source: https://phys.org/

Dr. Mohammad Mohidin, scientific director of the University of Maryland's animal-to-human transplant program, said: "If the latest research is proven to be effective, it will provide patients with a continuous supply of organs for transplantation."

Why use animal organs to save lives?

Previously, the organ transplants we are familiar with are usually allogeneic transplants: transplanting organs from human donors to people in need. But as mentioned at the beginning, this approach has a big problem: organ shortage. According to data from the World Health Organization (WHO), less than 10% of the global organ transplant demand can be met each year. In the United States, an average of 10 people die every day because they cannot wait for a suitable transplant organ; in my country, 300,000 people are waiting for a suitable organ, but only about 16,000 organs can be successfully transplanted each year.

It is precisely because of this huge imbalance between supply and demand that xenotransplantation has shown great value. Xenotransplantation refers to the transplantation or infusion of living cells, tissues or organs of non-human animals into the human body. Since animals can be raised in batches, the source of donors for xenotransplantation will be greatly expanded.

In fact, this medical method, which sounds very advanced, has been tried by people hundreds of years ago. In 1667, French doctor Jean-Baptiste Denis transfused lamb blood into a 15-year-old boy and cured his high fever. This is also the earliest recorded case of blood transfusion.

Schematic diagram of blood transfusion in the 17th century (Image source: Chirurgia infusoria, placidis cl. virorum dubiis impugnata [with text of their letters], cum modesta, ad eadem, responsione. [Pt. I] / [Johann Daniel Major].)

In the 20th century, people began to try xenotransplantation of organs, including kidneys, hearts, livers, etc. However, people initially favored primates, such as chimpanzees and baboons, because they are closely related to humans.

However, people gradually discovered that primates, which seemed to be the most suitable donors for human organ transplantation, had many defects. In 1984, an American baby girl named Stephanie Fae Beauclair, who suffered from hypoplastic left heart syndrome, received a heart from a baboon and became the first baby to receive a xenotransplant. But after only 21 days, she died of immune rejection.

This incident poured cold water on xenotransplantation, and the baby girl became the famous "Baby Fae". In addition to the rejection reaction that still exists, there are other problems with non-human primates as donors: they are prone to ethical controversy, the risk of cross-species transmission of pathogens is high, they are difficult to raise and breed, and the organ size does not match, etc.

Since the 1990s, researchers have gradually turned their attention to an animal that we are more familiar with: pigs. Pigs have a series of advantages, such as large litter size, fast maturity, body size and physiological characteristics that are closer to humans, and a lower risk of cross-species pathogen transmission, which makes them more valuable in practical applications.

Image source: Pixabay

In fact, as early as 1838, American doctor Richard Sharp Kissam performed the first human xenotransplantation on an Irishman, and the donor was a pig. Transplantation of these non-cellular structures will not cause an immune response in the human body, and xenotransplantation of corneas and heart valves has been used clinically.

Bennett, who received a pig heart transplant this time, also used a pig heart valve 10 years ago.

Transplant surgery achieves new breakthrough

According to the University of Maryland Medical Center, the pigs used in the transplant surgery have been genetically modified - researchers have "knocked out" three genes in the pigs that would cause humans to reject pig organs; another specific gene has been "knocked out" to prevent excessive growth of pig heart tissue transplanted into the human body.

In addition, the researchers inserted six relevant human genes into the pig genome to make its organs more acceptable to the human immune system. At the same time, the surgical team also used anti-rejection drugs, which are designed to suppress the human immune system and prevent organ rejection.

The center said that this transplant operation is the first to show that a genetically modified animal heart can function like a human heart after being transplanted into the human body, and the body will not immediately reject the animal heart. In the next period of time, the team will continue to observe the patient to determine whether the xenotransplantation technology can continue to work and save lives.

Researchers say that while it is not yet known whether the procedure actually works, it marks an important step toward using animal organs to save human lives, something scientists have been working toward for decades.

Is the new era of organ transplantation, where xenobiotic animal organs replace human organs, really coming? This still requires scientists to continue to explore.

Reference link: https://www.umms.org/ummc/news/2022/first-successful-transplant-of-porcine-heart-into-adult-human-heart

https://nyulangone.org/news/progress-xenotransplantation-opens-door-new-supply-critically-needed-organs

https://nyulangone.org/news/nyu-langone-health-performs-second-successful-xenotransplantation-surgery

https://www.fda.gov/vaccines-blood-biologics/xenotransplantation

https://www.sciencedirect.com/topics/medicine-and-dentistry/xenotransplantation

https://www.frontiersin.org/articles/10.3389/fimmu.2019.03060/full

https://en.wikipedia.org/wiki/Baby_Fae

https://www.sciencedirect.com/science/article/abs/pii/S2173507717300297

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/627415

Comprehensive sources: Xinhuanet, Science and Technology Daily, Global Science, Qilu Evening News, etc.