We are one step closer to the era when alien animal organs are used for human transplantation.
The University of Maryland School of Medicine said at a news conference monday that a 57-year-old Maryland man, David Bennett, was doing well three days after receiving the first transgenic pig heart transplant. Bennett also became the first person in the world to receive a heart transplant from a genetically modified pig.
David Bennett suffers from advanced heart disease, and pig hearts are "the only option available at the moment." After reviewing his medical records, Bennett was deemed ineligible for a traditional heart transplant or an artificial heart pump.
On December 31, 2021, the U.S. Food and Drug Administration approved an emergency authorization for the procedure to the University of Maryland Medical Center.
Dr. Bartley Griffith, a surgeon at the University of Maryland School of Medicine, said in a statement, "There simply aren't enough human heart transplant donors [right now] to meet a long list of potential recipient needs." "We are proceeding cautiously, but we are also optimistic that this world-first surgery will provide patients with important new options in the future."
Notably, the heart transplanted into Bennett's body, the genetically modified pig from revivic pharmaceutical company Revivicor, Blacksburg, Virginia, this 1-year-old "donor pig" weighing 240 pounds, has been genetically modified, and the staff fed it for organ transplant purposes.
According to public information, Revivicor is the world's largest pig cloning company, with strong gene editing technology and cloning technology. On December 14, 2021, the FDA approved the first intentional genomic alteration (IGA) in a domestic pig strain for human food and potential therapeutic uses— designed to eliminate alterations in α-galactose on the surface of porcine cells. Revivicor's goal is to produce genetically modified pigs (GE) to provide human-compatible cells (i.e., islets) to treat diabetes as well as organs and tissues for use in transplant surgery (xenotransplantation).
Surgeon Griffy with patient Bennett (from CNN Health)
"This is a watershed event", Dr. Lee, Chief Medical Officer of the United Organ Sharing Network Organization David Klassen commented, "The door to a new era is opening, and I firmly believe it will bring about a major change in how organ failure is treated". He also added that there are still many hurdles to overcome before such surgeries are widely used, and given the rejection response of organ transplants, they can occur even in well-matched people's kidney transplants.
The data shows that 17 people die every day in the United States while waiting for organ transplants, and the number of people on the waiting list exceeds 100,000. Organ shortages are a global problem, and although organ donation exists worldwide, very few organ transplants can be achieved. In China, about 1 million organ failure patients each year, 300,000 of whom are in urgent need of organ transplantation, but only about 20,000 people have access to transplants.
Based on this situation, researchers around the world are trying to solve the shortage of organ transplants in a variety of ways, of which Xenotransplantation is the most promising application.
Li Lei, who knows that he is certified as a doctor of biology of the Chinese Academy of Sciences, wrote that first of all, xenotransplantation should consider the matching of biological size, such as cats, dogs, mice, etc. and the human body size is too large, and secondly, the organs are relatively low, under these conditions, pigs have become an important source of heterogeneous organs, and their body size is similar to that of humans, consistent with diet, similar metabolism, and relatively low.
As early as 2016, baboons transplanted with genetically modified pig hearts eventually survived for 945 days, and in 2019, transplanted genetically modified macaques survived for 499 days.
In addition to primate xenotransplantation, in October 2021, the Langni Health Center at New York University in the United States tested a special kidney transplant that transplanted a genetically modified pig kidney to a female patient who had died of brain death without immediate rejection. This operation is not intended to prolong the patient's life, but a technical verification test, similar to the previous primate xenotransplantation, all using ectopic transplantation, transplanting pig kidneys to the blood vessels of the patient's thighs. The technical trial ended after 54 hours of continuous observation, and the donor pigs used in the trial also came from the regenerative pharmaceutical company Revivicor.
Before a xenotransplantation, the most important step is genetic modification. Although xenotransplantation has brought more vitality to humans, xenograft rejection is a difficult obstacle to overcome, mainly including ultra-acute rejection (HAR), acute vascular rejection (AVR), and acute cellular rejection (ACR).
Among them, α-gal (α-1,3-galactose transgenase, that is, GGTA1P gene) can lead to the occurrence of ultra-acute rejection of xenotransplantation, once the ultra-acute rejection reaction is triggered, the organ will necrosis within a few hours, and the patient will die quickly.
In this pig heart transplant, a total of 10 genes were modified, first of all, 3 genes that caused the human immune system to reject pig organs were removed from the donor pig, and 1 gene was removed to prevent the overgrowth of pig heart tissue; followed by 6 human genes responsible for immune acceptance.
Diagram of the swine heart transplantation procedure (from CNN Health)
Li Lei said in his article that to achieve xenotransplantation, several basic problems need to be solved, in addition to immune rejection, the humanization process cannot be ignored, that is, the use of human genes to replace the genes of pigs, otherwise there will be problems with the transplanted organs themselves, or the transplantation is only a piece of meat.
For now, Bennett's doctors also need to monitor him for days to weeks to see if the transplant will provide life-saving benefits. He will be monitored for immune system problems or other complications.
Dr. Philip, who knows that he is certified as a doctor of surgery at Shanghai Jiao Tong University, said that the pig heart human transplantation is a step closer to the former pig kidney human transplantation - 10 genes have been modified, both deleted and imported, and theoretically, the pig heart can be stored in the human body for a longer period. "But how long a patient can live is also related to many other factors, not entirely related to rejection, such as the patient's previous health status, nutrition, infection and other factors." At the same time he wrote.
At present, the domestic companies dedicated to xeno organ transplantation include Qihan Biologics, Zhenzhen Medical, Gailand Biotechnology Co., Ltd., Hunan Sainuo Biological, Chengdu Zhongke Og, Hangzhou Hering Pharmaceutical, etc., among which Sainuo Biologics is listed on the New Third Board.
(Titanium Media App editor Yang Yaru synthesized from Sohu News, Zhihu, Financial Associated Press, etc.)