For roughly six months, fully functioning pig hearts beat inside the chests of two Anubis baboons. Genetic modifications to the pig hearts along with a new transplant technique are credited with the longest-yet survival after such a transplant, researchers report December 5 in Nature. Previously, the longest a baboon lived after such a procedure was 57 days.
Another two baboons in the study lived at least three months with pig hearts and were in good health during that time, says Bruno Reichart, a cardiac surgeon at Ludwig-Maximilians-Universität in Munich. The baboons hopped and climbed around their enclosures. Some enjoyed eating mangoes and eggs, and watching TV programs like “Tom and Jerry” and “Alvin and the Chipmunks,” he says.
This work brings scientists closer to the goal of successfully transplanting life-supporting pig organs into humans, says Luhan Yang, chief scientific officer of eGenesis, a Boston company developing ways to transplant organs between different species in order to ease organ shortages (SN: 10/4/17, p. 26). “Of course, it’s still early, but we’re one step closer to the clinical application,” says Yang, who was not involved in the study.
The pigs were engineered to produce a human version of two proteins — CD46, which blocks an immune response that pokes holes in foreign cells, and thrombomodulin, which prevents blood from clotting after surgery. Researchers also ensured that the pigs couldn’t make alpha-gal sugars, which coat the cells of all mammals except monkeys, apes and humans. Those sugars can provoke the immune system to attack organs transplanted from pigs into humans and other primates.
Researchers fine-tuned the transplant procedure over the course of three trials involving 14 baboons, and found that two steps in the process were key to its success. First, instead of transporting the organs in a cold solution — as is standard practice in human-to-human transplants — scientists hooked the hearts up to a machine that steadily pumped an oxygenated mixture of blood and nutrients. Transporting hearts in an ice bath can cut off oxygen to the organs. Repeated infusions of blood prevented the hearts from eventually failing.
Next, the scientists aimed to prevent the pig hearts from growing too big for the baboons. After swelling from the operation subsides, a transplanted heart continues to grow and can damage nearby organs. So the researchers decreased the baboons’ blood pressure, and weaned the monkeys off anti-inflammatory cortisone steroids earlier. The team also gave the baboons a medication that limits the heart’s growth by keeping blood platelets from building up.
Of the five baboons in the final experiment, two remained healthy through the three-month trial period and one had to be euthanized early after developing a blood clot. One of the two allowed to live six months eventually developed liver damage after being weaned off medication while the other remained relatively healthy.