Pigs With Human Genes
In a step toward creating herds of pigs that could provide organs for transplanting into humans, Italian researchers manipulated swine sperm to make an animal strain that carries human genes in the heart, liver and kidneys.
Researchers at the University of Milan mixed swine sperm with the DNA of a human gene called decay accelerating factor, or DAF, and then used the modified sperm to fertilize pig eggs. The eggs were implanted into sows to produce litters of pigs that carried the human gene.
"What we obtain at high efficiency and low cost is genetically modified pigs expressing the human protein," said Dr. Marialuisa Lavitrano, a University of Milan researcher and first author of the study appearing Tuesday in the Proceedings of the National Academy of Sciences.
Lavitrano said that 205 piglets in 20 litters were produced using the modified sperm technique and the human genes were present in 20 to 50 percent of the young. Tests showed that the human genes were present in the animals' central organs and that the human genes would be passed along to later generations of pigs.
Organs from the test animals are not ready for transplantation into humans because there are still pig genes that would cause the organs to be quickly rejected, said Lavitrano. But she said the technique shows that by adding human genes to pig sperm it is possible to develop animals with organs that will not be rejected by the human immune system.
"They could be the starting point for new transgenesis (gene transfer) experiments," she said.
Lavitrano said that five to seven other pig genes will need to be silenced or replaced by human genes before useful organs could be harvested from the animals.
"With our efficiency we think we can add the other genes and breed the animals in about two years," she said.
Medical scientists have been working to change swine genes so that modified animals could be used to make organs that would be tolerated by the human body. The goal is to create a special strain of pigs that could make organs that could be used to replace ailing livers, kidneys and hearts in humans. It's hoped that the use of pig organs would relieve the shortage of human organs available for transplant. It has been estimated that about 4,000 people die each year while awaiting donor organs.
For this xenotransplantation to work, the organs would have to be tolerated by the human immune system. Otherwise, the transplanted organs would be destroyed by the immune system within a short time.
Other researchers, using another technique, have eliminated one of two genes that make a sugar called alpha-1-galactose. This gene prompts an acute rejection by the human immune system. The researchers now are attempting to remove a second sugar gene that also causes rejection.
Dr. Randall S. Prather, a pig reproduction physiologist at the University of Missouri and a researcher who helped eliminate the alpha-1-galactose gene in one strain of pigs, said the Lavitrano study is an advance because it demonstrates a simple way to add genes to the swine DNA. But it has limitations in developing pigs for xenotransplantation, he said.
"You can add a gene, but you cannot alter or remove a gene using this technique," said Prather. It is known that some other genes will have to be altered or removed in order to create animals for the xenotransplantation of organs, he said.
In the Italian study, the researchers inserted in the pig DNA a human gene for DAF, a gene that has been shown to help overcome rejection of pig organs in nonhuman primates.
Pig parts have been used to replace heart valves in humans, but replacing whole organs represents a significantly more complex challenge.
One of the concerns about xenotransplantation is the possibility that unrecognized swine viruses could be transferred into human patients along with the transplanted organ, experts say.