Human kidney transplantation into pigs for the first time | Medical research
Scientists have succeeded in transplanting human kidneys into pigs, which raises the possibility of transplanting human organs into animals.
The research involved creating human and porcine chimeric embryos containing a mixture of human and porcine cells. When transferred to surrogate pig mothers, the developing embryos were shown to have kidneys containing mostly human cells, marking the first time scientists have transplanted a solid, humanized organ into another animal.
“Mice organs were produced in mice, and rat organs were produced in mice, but previous attempts to transplant human organs into pigs were unsuccessful,” said lead researcher Liangxu Lai, of the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences. Science and Wuyi University. “Our approach improves incorporation of human cells into recipient tissues and allows us to grow human organs in pigs.”
The kidneys were not entirely human, as they contained blood vessels and nerves made mostly of pig cells, meaning they could not be used for transplantation in their current form. It is not clear whether the challenge of making an entire human organ can be accomplished with current genetic engineering techniques.
Professor Dusko Ilic, a stem cell scientist at King’s College London who was not involved in the research, described the work as groundbreaking but said no clinical applications would happen in the foreseeable future. “As the authors acknowledge, there are a lot of challenges,” he said. “Will this approach be the ultimate solution? Only time will tell.”
Aside from the kidneys, pig cells dominated the fetuses, with very few human cells in the brain or central nervous system. The possibility of a humanized brain is a serious ethical concern for research involving hybrid embryos and one reason for the tight legal restrictions on research in many countries.
In the UK, human embryonic cells are allowed to be inserted into animal embryos, but embryos cannot be transplanted into an animal mother for further development.
Previous attempts to create human-pig hybrids have faltered because pig cells tend to outpace human cells during development, meaning the resulting chimera is almost entirely pig. The latest work, published in the journal Cell Stem Cell, overcomes this problem by genetically engineering a single-celled pig embryo so that it lacks two genes essential for kidney development. This created a niche within the embryo that could be filled with human embryonic stem cells that were fused into the pig embryo.
After being grown in the laboratory, the chimeric embryos were transferred into 13 surrogate pigs. After 25 or 28 days, the pregnancy was terminated, and the embryos were extracted and evaluated. The fetuses had kidneys that were structurally normal for their stage of development, showing the tubes that would eventually connect the kidney to the bladder, and consisted of 50-60% human cells. Very human neurons are found in the brain and spinal cord.
Professor Chen Dai of the Guangzhou Institutes of Biomedicine and Health, another senior author, said: “We found that if you create a niche in the pig embryo, human cells will naturally enter these spaces.”
The scientists said the ability to incubate an entire human kidney inside a pig is likely to take many years. “Maybe we need to engineer pigs in a more complex way, and that also brings some additional challenges,” said Miguel Esteban, also from the Guangzhou Institute and one of the senior authors.
The main challenge is to allow human nerves and blood vessels to develop within the target organ without developing neurons in the central nervous system that would give rise to a human brain. “Even in theory, it is not clear how you can do this,” said Ilyich.