Scientists have grown humanised kidneys in pigs, raising the prospect of human organs being grown inside animals.
The research involved creating human-pig chimeric embryos containing a combination of human and pig cells. When transferred into surrogate pig mothers, the developing embryos were shown to have kidneys that contained mostly human cells, marking the first time that scientists have grown a solid humanised organ inside another animal.
“Rat organs have been produced in mice, and mouse organs have been produced in rats, but previous attempts to grow human organs in pigs have not succeeded,” said the senior author Liangxue Lai, of the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences and Wuyi University. “Our approach improves the integration of human cells into recipient tissues and allows us to grow human organs in pigs.”
The kidneys were not entirely human as they included vasculature and nerves made mostly from pig cells, meaning they could not be used for transplantation in their current form. It is not clear whether the challenge of making a wholly human organ would be achievable with current genetic engineering techniques.
Prof Dusko Ilic, a stem cell scientist at King’s College London, who was not involved in the research, described the work as pioneering but said any clinical applications would not happen in the foreseeable future. “As the authors admitted, there are plenty of challenges,” he said. “Will this approach prove to be the ultimate solution? Only time holds the answer.”
Aside from the kidneys, the embryos were dominated by pig cells, with very few human cells in the brain or central nervous system. The potential for a humanised brain is a serious ethical concern for research involving hybrid embryos and one of the reasons for tight legal restrictions on research in many countries.
In the UK, introducing human embryonic cells into animal embryos is permitted, but the embryos cannot be implanted into an animal mother for further development.
Previous attempts to create human-pig hybrids have foundered because pig cells tend to outcompete human cells during development, meaning the resultant chimera is almost entirely pig. The latest work, published in Cell Stem Cell, overcame this by genetically engineering a single-cell pig embryo so that it lacked two genes needed for kidney development. This created a niche within the embryo that could be filled by human embryonic stem cells that were integrated into the pig embryo.
After being cultivated in the lab, the chimeric embryos were transferred to 13 surrogate sows. After either 25 or 28 days, the gestation was terminated and embryos were extracted and assessed. The embryos had structurally normal kidneys for their stage of development, showing the tubules that would eventually connect the kidney to the bladder, and were composed of 50-60% human cells. Very human neural cells were found in the brain and spinal cord.
“We found that if you create a niche in the pig embryo, then the human cells naturally go into these spaces,” said Prof Zhen Dai of Guangzhou Institutes of Biomedicine and Health, another senior author.
The scientists said that being able to incubate a fully human kidney inside a pig would be likely to take many years. “We would probably need to engineer the pigs in a much more complex way and that also brings some additional challenges,” said Miguel Esteban, also of the Guangzhou institute and a senior author.
A central challenge would be to allow human nerves and vasculature to develop within the target organ without nerve cells developing in the central nervous system that could lead to a humanised brain. “Even theoretically it’s not clear how you’d do that,” said Ilic.
