On October 20 this year, the Langone Medical Center of New York University announced that the surgical team of the center successfully transplanted a pig kidney with a gene knockout of donor-specific thymus tissue into the groin of a human brain-dead subject. It has been reported that the pig kidneys play a role immediately, producing a large amount of urine within minutes, which is a key function of the kidneys. In addition, the subjects had normal levels of creatinine in their blood, another sign of good kidney function. The experiment was terminated after 54 hours, during which time the kidneys did not exhibit macroscopic properties associated with rejection.
This shows that the breakthrough trial was a success. At the same time, it has also aroused people's attention to the huge potential of xenotransplantation.
Less than two months after the first breakthrough surgery, on December 13, local time, the Langone Health Center of New York University used genetically engineered pig kidneys to perform a second experimental xenotransplantation operation. This surgery marks another advance in the field of application of potential alternative organs.
Leading the second surgery was still Professor Robert Montgomery, chair of the Department of Surgery at New York University's Rothman School of Medicine and director of the Gurney Health Center Transplant Institute. He transplanted a pig kidney missing the α-gal gene into a recently deceased ventilator-supported human donor provided by LiveOnNY.
Robert Montgomery
LiveOnNY, a nonprofit organization responsible for organ donation in the New York area, helped identify a generous whole-body organ donor to help advance this landmark study.
Professor Montgomery said: "We have completely replicated the process of the first surgery, demonstrating that these genetically engineered organs can become a source of renewable organs for many of the world's waiting groups to save lives. There is still a lot of work to be done before we start experimenting in vivis, but our initial success gives us hope. ”
The surgery is part of an ongoing study conducted on November 22, 2021 at New York University's Langone Research Lab. The pig kidney comes from a "GalSafe" pig designed by Revivicor, a subsidiary of United Therapeutics in the United States. "GalSafe" pigs genetically engineer the α-galoglycan gene on the surface of pig cells, which causes the body to produce a rapid rejection of pig organs. The pig's thymus gland, which is responsible for "educating" the immune system, has fused with the kidneys before transplantation.
During the 54-hour study, the pig kidneys were attached to blood vessels outside the thighs and abdomen and covered with protective covers for observation and renal tissue sampling. Urine production and creatinine levels are normal, and these key indicators are comparable to those found in human kidney transplantation. Throughout the procedure and subsequent observation, there were no signs of rejection.
Montgomery said: "Once again, we are making progress on single-gene knockout xenotransplantation, and through further research and replication, this could be the way to save thousands of lives every year." ”
Recently, however, Professor David K.C. Cooper of the Center for Transplant Science at Harvard Medical School published some of his thoughts on the experiment in Xenotransplantation.
He believes that the information provided due to this experiment is very limited, but the following points are worth noting:
1. A large number of in vivo studies conducted in non-human primates predict that the kidneys of pigs will play a role immediately;
2. A large number of in vitro studies predict that genetically engineered pig kidneys will not be rejected in the first few days after transplantation into human subjects;
3. Genetically engineered pig kidney is not the best choice for clinical transplantation, and the transplantation of three gene knockout (TKO) pig kidney may be more meaningful;
4. It is meaningless to transplant "thymic cells" without pretreatment and follow-up for several months before transplantation;
5. Because the natural kidney is retained, it is difficult to determine whether the function of the graft is sufficient to maintain life;
6) The experiment was published to the media, rather than in a peer-reviewed medical journal (although it is expected to be published later), suggesting that the experiment was primarily intended to draw attention to the enormous potential of xenotransplantation. In this regard, the experiment was successful.
Since brain-dead subjects maintain metabolic and hemodynamic homeostasis for a very limited amount of time, the value of experiments on such subjects remains very limited. He hopes that any similar experiments in the future will be more clinically appropriate. But the experiment sparked public attention on xenotransplantation and therefore has significant benefits for the future of the xenotransplantation field.
Source | China Biotechnology Network
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