In hopes of generating organs for human transplants, scientists have grown middle-stage kidneys made partly of human cells inside pig embryos.
The achievement is “an important and interesting step,” but such transplants are still many years away, Massimo Mangiola, a transplant immunologist at New York University who did not contribute to the findings, tells Science News’ Amanda Heidt.
Still, the new achievement “hints that the ultimate goal of developing human organs in other mammals might be possible,” Juan Carlos Izpisúa Belmonte, a developmental biologist at Altos Labs who was not involved with the research, tells Science’s Mitch Leslie. It “is a big step forward in the field.”
And for kidneys, in particular, growing the organs would be valuable: More than 106,000 people in the United States are currently on the national transplants waiting list for organs from deceased donors, and of these patients, 92,000 are awaiting a kidney, according to the American Kidney Fund. Most people wait three to five years to receive a donation of this blood-filtering organ, and every day, an estimated 13 people die before they can get a transplant. So, scientists are looking for alternatives, including generating organs inside other mammals.
Previously, researchers have achieved interspecies organ generation between mice and rats for organs including the pancreas, thymus and kidney, according to the new study, published last week in the journal Cell Stem Cell. This summer, researchers successfully transplanted a genetically modified pig kidney into a brain-dead patient. They’ve also grown human skeletal muscle and blood vessel lining in pig embryos, per Science. But no solid organs with human cells had previously been created inside another creature, according to the study.
To achieve this, the team turned off two genes in the pig embryos that cause the development of kidneys, writes New Scientist’s Alice Klein. Then, they genetically tweaked human stem cells in order to make them more likely to survive in the pig embryos and added these cells to the embryos.
The researchers next transferred 1,820 pig embryos with human cells into sow surrogates. After 25 days, they collected two normal embryos and four degenerating ones, and they extracted an additional three normal embryos after 28 days. In the normally developing embryos, human cells made up between 50 and 65 percent of the kidneys.
“It is remarkable to see that about 60 percent of the primordial pig kidney contained human cells,” Jun Wu, a stem cell biologist at the University of Texas Southwestern Medical Center who did not contribute to the findings, tells Wired’s Emily Mullin.
Still, the study has some drawbacks. In early development, embryos only grow temporary kidneys—and the kidneys that would be used for organ transplants are a different kind that forms later, Science writes. The human stem cells also grew into only a couple of the more than 70 human kidney cell types, per Science News, and a completely human organ would likely be needed for transplant, since pig cells may be rejected by the body.
Paul Knoepfler, a stem cell biologist at the University of California, Davis, who did not contribute to the findings, tells Wired that two of the human genes the researchers edited could cause cancer if overexpressed, something that would need to be tested in the organs grown in pigs.
The research could also cause ethical quandaries if the pigs were brought to term and the human cells got into their brains and reproductive cells, the team writes. In the new study, the embryos’ brains and spinal cords did have some cells from humans.
Researchers may need to genetically alter the human cells in the future to prevent this spread into other parts of the pigs, Miguel Esteban, a co-author of the study and stem cell biologist at the Guangzhou Institutes of Biomedicine and Health, tells Science. However, Mangiola tells Science News that the human neurons in the embryos seem random and therefore probably wouldn’t lead to human brains.
To further the research, the team has received approval to let the embryos grow for up to 35 days, per New Scientist.
“The ability to generate human organs in pigs would make a significant impact in reducing the number of patients on a [transplant] waiting list in the United States and around the world,” Mary Garry, a professor of medicine at the University of Minnesota who did not contribute to the paper, tells Wired.