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Mice cured of diabetes by cells grown inside rats — are humans next?

Mice cured of diabetes by cells grown inside rats — are humans next?

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‘A remarkable scientific achievement’

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On the far left, the rat-mouse chimera created for the study.
On the far left, the rat-mouse chimera created for the study.
Tomoyuki Yamaguchi

It’s possible to grow organs of one species inside an animal of another species and then transplant that organ to cure disease, according to a study published today in Nature. In this case, mouse pancreas cells were grown in rats, then transplanted into mice to reverse diabetes. The new research opens the possibility of one day creating human organs inside animals like pigs or sheep that could then be transplanted back into needy patients.

“A remarkable scientific achievement”

To create the mouse pancreases, scientists first genetically engineered rats to lack a gene that’s key to developing the organ. These engineered rat embryos were then injected with mouse stem cells that can develop into any tissue or organ in the body. When the embryos grew into rats, the animals had a pancreas made up almost entirely of mouse cells. The scientists then removed the pancreas, isolated clusters of insulin-producing cells, and transplanted them into diabetic mice. The results were surprising, lead author Hiromitsu Nakauchi of Stanford University School of Medicine wrote in an email to The Verge. The transplanted cells reversed the mice’s diabetes and kept sugar levels down for one year. The mice didn’t reject the cells, even if they were given anti-rejection medication for only five days after the transplant.

Much more research needs to be done to make these functional interspecies organs a reality for people, including research into the ethics of this idea. But today’s study is “a remarkable scientific achievement,” Timothy Kieffer, a professor of cellular and physiological sciences and surgery at the University of British Columbia, who didn’t work on the study, wrote in an email to The Verge. And its implications for the future are enormous.

There are about 120,000 Americans who are currently on the waiting list to receive a lifesaving organ transplant, according to the US Department of Health and Human Services. Because of a shortage of donated hearts, lungs, and livers, more than 20 people die each day in the US on average waiting for a new organ. Some of the patients in need of transplants are people with type 1 diabetes, a chronic disease in which the pancreas produces little or no insulin, a hormone that controls sugar levels in the blood. These patients need insulin-producing cells from human donors, but because of the limited supply of donated organs, the procedure is rarely performed, says Kieffer. Instead, diabetic patients must inject insulin daily into their bodies through needles or pumps. That’s why today’s results are so important.

“I can see [this] work in the future.”

“There are not that many ways to generate a functional adult human organ for transplantation that can save many people’s lives,” says Qiao Zhou, an associate professor of stem cell and regenerative biology at the Harvard Stem Cell Institute, who didn’t work on the study. “This is one I think actually I can see work in the future.”

Some patients with diabetes have been infused with insulin-producing cells taken from pigs, Kieffer says. But the treatment didn’t work because the patients rejected the foreign cells. If in the future, pigs — or other animals — could be engineered to produce human cells that produce insulin, these cells could be then transplanted into patients with fewer risks of rejection.

Of course, before that happens, a lot more research needs to be done, Nakauchi says. Creating human organs inside an animal might not work as easily, because pigs, monkeys, and sheep are much more different from humans than rats are from mice. Some of the rats in the study also showed signs of rejection to the mouse pancreas growing inside of them. This breakdown of the host’s immune system needs to be studied and controlled, Kieffer says.

And then there are the ethical issues

And then there are the ethical issues, says Timo Otonkoski, a professor of medical stem cell research at University of Helsinki, who was not involved in the study. Some people might question the creation of human-pig hybrids, and opinions might change from country to country. Then there are more specific questions about these chimeras: if human stem cells are injected into animal embryos, some of these cells will also go into organs like the brain. What are the ethical implications of having pigs with part human brains? “The biological issues and the ethical issues are still in very preliminary phase,” Otonkoski says. “It’s still very hard to know if this has any real potential for human medicine. But it’s interesting biology and it’s interesting to explore whether these possibilities are real or not.”

This isn’t the first attempt at solving human diabetes by developing insulin-producing cells — other efforts have included growing these cells in the lab for transplants, or converting gut cells. But progress has been slow, and today’s study is not as far along as those efforts. If it’s possible to grow these cells inexpensively in the lab, human chimeras may not be necessary. And today’s work is a long way from showing that all organs can be grown in chimera animals. Still, today’s results may spark new interest in the field.