Combined Pig-Human Cells Spell Problems for Xenotransplantation
Pigs grown from fetuses into which human stem cells were injected have surprised scientists by having cells in which the DNA from the two species is mixed at the most intimate level.
It is the first time such fused cells have been seen in living creatures. The discovery could have serious implications for xenotransplantation – the use of animal tissue and organs in humans – and even the origin of diseases such as HIV.
The adult pigs that had received human stem cells as fetuses were found to have pig cells, human cells and the hybrid cells in their blood and organs.
"What we found was completely unexpected. We found that the human and pig cells had totally fused in the animals' bodies," said Jeffrey Platt, director of the Mayo Clinic Transplantation Biology Program.
The hybrid cells had both human and pig surface markers. But, most surprisingly, the hybrid cell nuclei were found to have chromosomal DNA that contained both human and pig genes. The researchers found that about 60 per cent of the animals' non-pig cells were hybrids, with the remainder being fully human.
Importantly, the team also found that porcine endogenous retrovirus (PERV), which is present in almost all pigs, was also present in the hybrid cells. Previous laboratory work has shown that while PERVs in pig cells cannot infect human cells, those in hybrid cells can. The discovery therefore suggests a serious potential problem for xenotransplantation.
The work also suggests a possible route of infection for other viruses that have crossed from animals to humans.
"Perhaps HIV managed to jump from primates to humans through infected blood from a bite, which allowed the stem cells from the two species to fuse," Platt told New Scientist. "When the genes recombined, perhaps the virus was reawakened."
Chimeric animals containing human cells have been created before. New Scientist reported in December on the growing of human liver cells in sheep. The work, by Esmail Zanjani and colleagues at the University of Nevada, Reno, aims to provide human tissue for transplantation into people.
"The new work is certainly very interesting," Zanjani told New Scientist. "But the question is how widespread and how many of these hybrid cells were found? If they are very rare – and we haven't found any in our experiments – then I don't think it is that important."
Zanjani says it is "possible" that HIV had spread to humans through a type of human-primate cell fusion, but adds that much more research needs to be done.
In Platt's experiments, the human stem cells were injected into the pig fetuses about a third of the way through gestation. In Zanjani's work, the cells were injected about halfway through.
The injections must be given after the body plan of the fetus has developed, but before the immune system is active. The former ensures the animals look like normal pigs and sheep. The latter prevents the human stem cells being rejected.
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