Human-pig 'chimera embryos' pave way to growing organs for transplants

Scientists have grown human cells inside pig embryos, a very early step toward the goal of growing livers and other human organs inside animals to transplant into people.

The cells made up just a tiny part of each embryo, and the embryos were grown for only a few weeks, researchers reported Thursday.

Such human-animal research has raised ethical concerns. The U.S. government suspended taxpayer funding of experiments in 2015. The new work, done in California and Spain, was paid for by private foundations.

Any growing of human organs in pigs is "far away," said Juan Carlos Izpisua Belmonte of the Salk Institute in La Jolla, California, an author of the paper in the journal Cell.

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He said the new research is "just a very early step toward the goal."

Even before that is achieved, he said, putting human cells in animals could pay off for studies of how genetic diseases develop and for screening potential drugs.

Animals with cells from different species are called chimeras. Such mixing has been done before with mice and rats. Larger animals like pigs would be needed to make human-sized organs. That could help ease the shortage of human donors for transplants.

The Salk team is working on making humanized pancreases, hearts and livers in pigs. The animals would grow those organs in place of their own, and they'd be euthanized before the organ is removed.

Most of the organ cells would be human. By injecting pig embryos with stem cells from the person who will get the transplant, the problem of rejection should be minimized, said another Salk researcher, Jun Wu.

Daniel Garry of the University of Minnesota, who is working on chimeras but didn't participate in the new work, called the Cell paper "an exciting initial step for this entire field."

The findings

Scientists used human stem cells, which are capable of producing a wide variety of specialized cells. They injected pig embryos made in the lab with three to 10 of those cells apiece, and implanted the embryos into sows. At three to four weeks of development, 186 embryos were removed and examined.

Less than one in every 100,000 embryonic cells was human, which still comes to about a million human cells, Wu said. That contribution is lower than expected, he said, "but we were very happy to see we actually can see the human cells after four weeks of development."

The cells generated the precursors of muscle, heart, pancreas, liver and spinal cord tissue in the embryos. The researchers said they plan to test ways to focus human cells on making specific tissues while avoiding any contribution to the brain, sperm or eggs.

Ethical issues

That addresses ethical concerns that the approach could accidentally lead to pigs that gain some human qualities in their brains, or make human egg or sperm.

There was no sign of that in the new research. The government, meanwhile, has signalled that it may lift the federal funding ban soon but impose extra oversight of any proposed work.

A pig might not always have to be brought to term, Belmonte and Wu said. Even a pig fetus might provide human pancreatic cells to treat diabetes, or kidney cells to repair injuries to that organ, they said.

The University of Minnesota's Garry said the research offers some direction about what kind of human stem cells will work best. And it shows a need for boosting the number of human cells that appear in the embryo, he said.

Hiromitsu Nakauchi of Stanford University said his own unpublished experiments with pig and sheep embryos also found a sparse contribution from injected human cells. That's a challenge for making organs, but it might be surmounted by focusing cells on doing that job, he said.

Ethics experts were also impressed by the results. "It really does give a green light to explore more," said Insoo Hyun of Case Western Reserve University in Cleveland.

Hyun said he understood why some people might object on moral grounds to making animals with human organs.

"It seems kind of creepy," he said. But "this is a strategy to help save human lives" and so it is justified if properly done, he said.