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Freak Chimeras - Now scientists create a sheep that's 15% human

UK Daily Mail | March 25, 2007
CLAUDIA JOSEPH

Scientists have created the world's first human-sheep chimera - which has the body of a sheep and half-human organs.

The sheep have 15 per cent human cells and 85 per cent animal cells - and their evolution brings the prospect of animal organs being transplanted into humans one step closer.

Professor Esmail Zanjani, of the University of Nevada, has spent seven years and £5million perfecting the technique, which involves injecting adult human cells into a sheep's foetus.

He has already created a sheep liver which has a large proportion of human cells and eventually hopes to precisely match a sheep to a transplant patient, using their own stem cells to create their own flock of sheep.

The process would involve extracting stem cells from the donor's bone marrow and injecting them into the peritoneum of a sheep's foetus. When the lamb is born, two months later, it would have a liver, heart, lungs and brain that are partly human and available for transplant.

"We would take a couple of ounces of bone marrow cells from the patient,' said Prof Zanjani, whose work is highlighted in a Channel 4 programme tomorrow.

"We would isolate the stem cells from them, inject them into the peritoneum of these animals and then these cells would get distributed throughout the metabolic system into the circulatory system of all the organs in the body. The two ounces of stem cell or bone marrow cell we get would provide enough stem cells to do about ten foetuses. So you don't just have one organ for transplant purposes, you have many available in case the first one fails."

At present 7,168 patients are waiting for an organ transplant in Britain alone, and two thirds of them are expected to die before an organ becomes available.

Scientists at King's College, London, and the North East Stem Cell Institute in Newcastle have now applied to the HFEA, the Government's fertility watchdog, for permission to start work on the chimeras.

But the development is likely to revive criticisms about scientists playing God, with the possibility of silent viruses, which are harmless in animals, being introduced into the human race.

Dr Patrick Dixon, an international lecturer on biological trends, warned: "Many silent viruses could create a biological nightmare in humans. Mutant animal viruses are a real threat, as we have seen with HIV."

Animal rights activists fear that if the cells get mixed together, they could end up with cellular fusion, creating a hybrid which would have the features and characteristics of both man and sheep. But Prof Zanjani said: "Transplanting the cells into foetal sheep at this early stage does not result in fusion at all."

Animal Farm is on Channel 4 at 9pm tomorrow


FLASHBACK: Pig-human chimeras contain cell surprise

NewScientist.com | 13 January 2004
Gaia Vince

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.

Nuclear mix

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."

Body plan

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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