The birth of five cloned piglets last week could significantly increase the success rate of pig-to-human organ transplantation, according to creators, PPL Therapeutics.
Previous research has indicated that rejection of animal cells and organs by the human immune system is partially due to the presence of the gene alpha 1,3 galactosyl transferase. The gene codes for an enzyme that adds a sugar to the surface of pig cells, flagging them up as foreign bodies.
A US subsidiary of PPL Therapeutics, who were also responsible for the creation of Dolly the sheep, used gene targeting to knock out a single copy of alpha 1,3 galactosyl transferase. Nuclear transfer was then used to create the five piglets.The first use of the new technology is likely to involve the production of islet cells for the treatment of diabetes. Such cells will be transplanted into primates initially, but the researchers say that human trials could start in around four years' time.
In addition to hyperacute rejection by the human immune system, other hurdles facing xenotransplantation include delayed rejection, coagulopathy and chronic T-cell-mediated rejection. Therefore, it may be necessary to add up to three more genes to the DNA of the knock-out pigs, the scientists report.Dr Alan Colman, director of research at PPL Therapeutics, said, "With one of the major technical hurdles and scientific risks overcome, the promise of xenotransplantation is now a reality, with the potential to revolutionise the transplant industry."
Dr Philip Dyer, President Elect of the British Transplantation Society, said, "Alpha galactosyl knockout pigs have been made before, what's new is that [PPL have] cloned them, which makes [production] easier." He said, "Of concern is the potential risk of transmission of porcine viruses," but added, "We would welcome any breakthrough that supports the safe and effective transplantation of animal organs to humans because of the great shortage of human organs for transplantation."