Five piglets have been cloned from an adult female in a significant milestone on the road to successful organ transplants from pigs to humans. The cloning paves the way for the next step towards pig derived xenotransplants—the production of modified or so-called knock-out pigs, whereby a specific gene linked to hyperacute rejection in humans has been inactivated.
PPL Therapeutics, which cloned the piglets, predict that the market for solid organs alone could be worth $6bn (£3.75bn), with as much again from cellular therapies like transplantable cells for insulin production in diabetic patients.
The next step for PPL, which carried out its pig cloning work at Blacksburg, Virginia, is to repeat the experiment but this time producing knock-out pigs. The gene to be inactivated is for a-1,3 galactosyltransferase, which is responsible for adding to pig cells a sugar group recognised by the human immune system as foreign, triggering an immune response leading to rejection in humans of the transplanted organ.
“PPL has built up the technical expertise to be the first to produce the type of pig which should become the industry standard for xenotransplantation—a pig lacking the a-1,3 galactosyltransferase gene, said Alan Colman, PPL's research director.
The company said it has also made considerable progress in other areas of its xenograft programme and that potential solutions for all four known causes of rejection have been devised and shown to work in cell based experiments
In addition to the gene knock-out technology designed to prevent hyperacute rejection, three more genes will need to be introduced into pigs or pig cells to control the causes of delayed xenograft rejection.
About 180000 people around the world are estimated to be currently waiting for an organ transplant, but fewer than 1 in 3 will receive a transplant because of the ever widening gap between supply and demand. Many see organs derived from pigs as a solution to the problem.
Imutran, based in Cambridge, United Kingdom, which has also been working on overcoming hyperactive rejection (but by breeding transgenic pigs), described the PPL result as interesting. “It is potentially a useful technology to develop new lines of pigs for xenotransplantation. However, the next step is to see if the technology can be applied to developing genetically modified animals whose organs can be transplanted into humans without being rejected,” said a spokesman.
Mark Walport, professor of medicine at Imperial College, London, said, “The ability to clone pigs is a significant advance, but it is only one of a number of steps that need to be taken. We are still a long way from successful xenotransplants because there are so many potential barriers.”
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AP PHOTO/DAVID JENNINGS
A New York state wildlife pathologist examines a dead crow for traces of the West Nile encephalitis virus. Public health doctors are worried that the virus, which killed seven people in New York City last year, will re-appear there this summer. A dead, red tailed hawk, discovered in Bronxville, a suburb of the city, was last week found to be carrying the virus, which is spread by mosquitoes from birds to humans.