Researchers have successfully incorporated human cells into a sheep embryo — the first step in a process that they hope may one day allow them to grow replacement organs in other animals. The advance is one of several recent ones in a burgeoning field that is raising ethical questions.
The bottom line: Advances in the past year are important proofs-of-principle that this is even a plausible approach but an organ hasn't been grown in a large animal.
"We’re a long way away from getting a human tissue in a pig or sheep," says Thorold Theunissen, a stem cell biologist at Washington University School of Medicine. "It's a tantalizing prospect and important that more experiments are done.”
The need: On average, 20 people in the U.S. die each day waiting for an organ and someone is added to the national transplant list every ten minutes, according to the United Network for Organ Sharing.
Key experiments to date:
- Last year, Hiro Nakauchi from Stanford University's School of Medicine and his colleagues reported they could inject mouse pluripotent stem cells — which are able to form all types of adult stem cells — into embryos of rats that lacked a key gene for the development of the pancreas. The embryo instead developed the organ from the mouse cells. After the rat-mouse chimeras grew into adults, cells from those pancreases were transplanted into diabetic mice and the researchers found the disease was reversed.
- Also in 2017, researchers reported incorporating human cells into a pig embryo with a relatively low efficiency of about one human cell for every 100,000 pig cells. Pigs are ideal because their organs are roughly the same size as humans and they grow fast.
- On Saturday, at the annual meeting of the American Association for the Advancement of Science, Nakauchi, Pablo Ross from UC-Davis and Daniel Garry from the University of Minnesota announced they had created a human-sheep embryo. In this scenario, they saw 1 human cell for every 10,000 sheep ones. "It’s still short of what we postulate would be necessary to grow a whole organ," Ross tells Axios. That, he says, requires a contribution closer to 1% of all cells in the embryo.
What's next: Determining where the cells are going in the embryo and what impact they are having, Ross says. He also wants to use animals that have been gene-edited with CRISPR to lack certain organs and see if that helps the introduced stem cells grow in the host embryo. Theunissen and others are trying to determine the best conditions of the stem cells for incorporating them into the embryos — and which embryos are the best hosts.
One ethical concern is that the introduced cells will migrate to the host animal's nervous system, sparking fears of humanizing animals. But Nakauchi says they've been able to direct the cells to specific regions. Ross, too, says it's unlikely because the host embryo is driving the process of development and a sheep or pig doesn’t have the anatomy or right conditions to support something like a human nervous system.
"We aren’t on the brink of seeing half-sheep, half-human animals. This research is going to go slowly because it is difficult to get the cells what you want them to do,"— Insoo Hyun, bioethicist, Case Western Reserve University's School of Medicine
Still, Ross says, "[W]e need to observe that with science and generate scientific information that will help us make a decision about this approach that we are comfortable with — if it works. ... The final decision will be up to the public."
The NIH currently doesn't fund research involving the transfer of human stem cells to large animal embryos. There is oversight at the university and institutional level — for example, the sheep embryos were allowed to grow for 28 days.
The big picture: Researchers have long tried to understand the environmental cues that turn stem cells into one cell type instead of another and then to replicate those signals in the lab — in hopes of developing therapies for Lou Gehrig's disease, strokes and other conditions. Stem cells remain a bit of a black box but some clues may come from these experiments, Theunissen says. "It's not just about the whole tissue but also the individual cells."