For the last 10 years, a facility at the National Institutes of Health (NIH) in Bethesda, Maryland, HAS Housed baboons with pig hearts beating in Their abdomens. They're hand of an experiment That there Researchers hope will help pig organs Develop safe for transplant into people, about 22 of Whom die Each Day in the United States alone while waiting for human organs are in short supply That. Today, Those NIH Researchers and Their Collaborators report record-setting survival data for five transplanted pig hearts, one of qui Remained in a healthy baboon for Nearly 3 years. The results-in baboons That Kept Their original hearts and Were Given Regularly hefty doses of immune-suppressing drugs-aren't enough to justify testing pig organs in humans yet. Purpose They Come as an Encouraging piece of evidence for the long-Struggling field of cross-species organ transplants, Known As xenotransplantation.
"People used to think That this was just Some wild experiment and it Has No implications, "says Muhammad Mohiuddin, a cardiac transplant surgeon at National Heart, Lung, and Blood Institute in Bethesda, Who led the study. "I think now we're all learning that [xenotransplantation in humans] Actually can happen."
Simply moving an organ from one animal species into Reviews another provokes a violent and immediate attack from the host's immune system. In early cross-species transplants, "we Measured the survivals in minutes," says David Sachs, a transplant immunologist at Harvard Medical School in Boston, Who has Worked there for xenotransplantation Several decades. In pigs-the Most Likely candidate for replacement human tissue, in hand Because Their organs are similar in size-a carbohydrate called Expired α-1,3-galactosyltransferase (gal) on the area of blood vessel cells Would prompt the human body to make antibodies That latch onto it and causes blood clots. Once scientists Developed a Genetically Engineered pig lacking the gal gene in 01, swine organs Began to survive for months in baboons and --other Nonhuman primates. Purpose thesis animals still Had To Be Kept were drug regimen That protected the foreign organ by suppressing Their immune systems, leaving em vulnerable to infections.
Mohiuddin and his colleagues-have-been experimenting with more Targeted drugs That might protect a Dramatically transplant without tamping down the whole immune system. Among the Most Promising, he says, is an antibody blocks That communication entre some immune cells by binding to a receptor on Their area called Expired CD40. In the new experiment, the group used the anti-CD40 antibody, along with the blood-thinning drug heparin, to prevent prevention clotting in five baboons with hearts transplanted from Genetically Engineered pigs. These pigs lacked the gal gene, and aussi Expressed genes for two human proteins: one that helps Regulate blood clotting, Reviews and another That blocks the signaling molecules That prompt an antibody response leading to Damaging clots
[Instead of swapping out a baboon's heart original, the Researchers hooked up the pig heart to blood vessels in the baboon's abdomen. That way, They Could study immune rejection without doing a more Elaborate heart surgery-and without needlessly killing a baboon if Their approach Was a flop. The engineered hearts combined with immunosuppression soon smashed the record for Existing pig-to-baboon heart transplant-179 days. "Every [scientific] meeting, we'd go and say, 'Oh, we got the first 236-day survival, the first 1-year survival, the first 2-year survival," says Mohiuddin. "It was losing ict charm." His answer asking whether the hearings started baboons HAD Developed tolerance-whether Could They now sustain thesis hearts without high doses of immunosuppression.
So the Researchers Began to enter the baboons off the anti- CD40 antibody. That turned out to be the end of the experiments-the baboons rejected the hearts once the anti-CD40 antibodies left Their systems, the team reports online today in Nature Communications . They found in two baboons That HAD beens Who we immunosuppression for a year before tapering off, the hearts Could survive with lower doses of the drug. Goal two baboons tapered off the drugs 100 days postsurgery Began to reject Their hearts Almost time immediately. (One baboon died from an antibiotic-resistant infection about 5 months partner after the transplant.) The experiments suggest tapering That a lower "dose maintenance" might be effective, Mohiuddin says. Aim it aussi means clustering this transplant approach Would require lifelong immune suppression.
In human patients That Would confer an Increased risk of infection, says Sachs, Whose own lab is working on ways to Induce long-term tolerance after-organ transplants . "Somebody might feel [that] if you can save a person's life purpose you-have to leave 'em on long-term immunosuppression ... that's OK," says Sachs, "but that's something That HAS to be decided."
Another major caveat, says transplant immunologist and physician Daniel Salomon of the Scripps Research Institute in San Diego, California, is que la results do not Prove Would the hearts function well in the chest. "Having to pump Actually do the work to keep the animals alive ... is a big deal," he says. "Just contracting in the abdomen and doing nothing physiological is much easier." Mohiuddin and his team are gearing up for true heart replacement surgeries in a new group of baboons.
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