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○Rgan transplants save lives, but because healthy specimens from suitable donors are in short supply, scientists are relying on the latest scientific advances rather than chance to create a more reliable replacement for diseased organs. I’m looking for a high way.
Introducing a pig that is bringing hope to the 10,000 people in the United States currently waiting for a liver transplant. On January 18, researchers from the University of Pennsylvania and the biotech companies eGenesis and OrganOx announced a major step toward one potential way to address this problem.They connected a brain-dead patient to a pig’s liver, which circulated the man’s blood for three days..
“It was amazing for me to see the system work,” says Dr. Abraham Shaked, a professor of surgery at the University of Pennsylvania who oversaw the experiment. “The brain-dead patient was in a very stable condition and we were very surprised to see that the pig’s liver was functioning outside the body for three days and looked much better.”
Scientists said their experiments with patients proved that genetically modified pig livers can act as a temporary replacement for human livers. In this first case, the brain-dead patient’s liver continued to function, but the researchers plan to test the system in brain-dead patients whose livers have been removed.
It is hoped that pig livers may one day serve as a temporary bridge to support patients on the transplant waiting list and those whose livers have weakened due to alcohol-related diseases and take time to recover on their own. ing. Eventually, livers may also be transplanted into humans.
How to use
This breakthrough is a combination of several scientific innovations. The pig donor was a clone created using the same process that produced the first cloned mammal, Dolly the sheep. The clones were created using pig cells that were gene-edited using CRISPR technology. The resulting pig liver was then connected to a perfusion device that pumped blood between the brain-dead patient and the pig’s liver.
Shaked said early tests showed that during the three days of the study, pig livers functioned much like human livers, drawing blood from patients and producing bile. Mike Curtis, CEO of EGenesys, the company that created the genetically engineered pigs, said patients also showed additive effects on other measures of liver function, such as bilirubin and lactate levels, which could lead to He said that suggests the pig’s liver was contributing to what the patient’s liver produced.
overcome rejection
Animal-to-human liver transplants, or xenotransplants, have been the holy grail for scientists since the 1960s. However, many such studies failed due to rejection. Organs between species are inherently incompatible. For example, when a pig’s liver is replaced with a human liver, microscopic blood clots form in the smallest blood vessels, destroying red blood cells and cutting off the blood supply to the transplanted liver.
One way to address the problem is to modify some of the genes in pig livers to make them less pig-like and more human-like, but the first such modified livers could not be produced using the technology available at the time. Only a limited number of genetic changes could be included.For example, in a 2017 study, scientists found that transplanted It was a single genetically modified pig liver to reduce its incompatibility with baboons, but the liver was ultimately rejected. However, one baboon survived for a month, suggesting that the technique may reduce the chance of rejection and extend transplant survival.
Since that work, the gene editing technology CRISPR has emerged as a powerful way to introduce multiple genetic changes with relative ease. In this study, eGenesis scientists used his CRISPR to make not one, but 69 edits to the pig’s genome. Three of the edits removed the most pig-like proteins that could activate human systems to reject the liver, and seven edits added human genes to the pigs. 59 to inactivate porcine retroviruses that can cause problems in the liver and in humans. “Before CRISPR, there was no easy way to make this many edits,” Curtis says.
The future of pork liver
Dr. Sheikh says this single-patient study is just the beginning of what xenotransplantation can accomplish. The liver has two main roles in the body. One is regulating important enzymes and substances such as glucose and cholesterol, the other is filtering toxins from the blood. This experiment focused on the latter, but in the coming years more sophisticated pig livers will eventually be able to perform some of the organ’s more complex functions in human patients.
The research needed to get there is already underway. Sheikh is optimistic that, after further testing, the first liver failure patients will be able to try the system by the end of the year. Hopefully, by connecting it to a pig’s liver, it will either recover on its own or be preserved while waiting for a transplant. “Based on what I saw, I was encouraged,” he says.
