A Wisconsin company announced the birth of three cloned pigs last Thursday that have internal organs with genetically modified traits that increase similarity to human organs.
Infigen, Inc. of Deforest became the second firm to develop pigs without a gene that attaches a specific carbohydrate to the surface of a pig’s cell. Because humans and primates do not have this carbohydrate on their cell surfaces, a pig organ transplanted into a human or ape is immediately recognized and rejected.
The gene was “knocked out” in cell cultures and then the nucleus of the cell was used to make cloned embryos. The embryos were transferred to recipient sows and the cloned “knockout” piglets were born about four months later.
Infigen’s vice president of development, Erik Forsberg, said that xenotransplantation, or the transplantation of animal organs into humans, was still a long way off, but the company’s accomplishment would make the concept more viable.
“We used an inbred strain of miniature swine,” Forsberg said. “These miniature swine grow to about 160 to 180 pounds which is close to human weights. Commercial pigs grow to about 800 to 1000 pounds and the fear is that if you put an organ from a commercial pig into a human it might grow too large.”
Forsberg said a future transplant from a miniature swine would not transplant retroviruses to humans like tests show commercial pigs would do.
Because of the close physiology of humans and pigs, genetically altered swine have been considered for transplantation of the kidney, heart, pancreas, lung and even liver to humans.
Currently, the University of Wisconsin is working with pancreatic islet cells that produce insulin. UW scientists are taking small parts of pig pancreases and knocking out genes similar to those knocked out in Infigen’s cloned baby pigs.
Hans Sollinger, chair of organ transplantation at the UW, said drugs to prevent the rejection of the pig pancreatic cells would allow the cells to possibly be used as a cure for diabetes.
Sollinger said Infigen made a major contribution to the possibility of future xenotransplantation, but that there was no way their accomplishment is the end of the road.
“Pigs and man have a number of incompatibilities. Different enzyme and coagulation systems, for example,” Sollinger said. “What [Infigen] has done is removed one component of the cell membrane. It is only one of many hundred components that need to be worked through.”
Sollinger said the elimination of the carbohydrate cell acts to only mitigate one type of rejection.
Forsberg agreed that there were many difficulties before a human receiving an organ transplant from any kind of animal could be realized.
“There may be additional barriers to overcome which may delay the prospects for xenotransplantation into humans,” Forsberg said. “Nevertheless, xenotransplantation is the only foreseeable means to overcome the shortage of organs.”
Before an organ can be transplanted into a human from an animal, successful trials in primates would have to be conducted, according to Forsberg. He said scientists would then have to wait for approval of the Food and Drug Administration and expected that process to take about five years.
Infigen worked in collaboration with Immerge BioTherapeutics of Boston, Mass., in cloning the pigs.
