Scientists have grown humanized kidneys in pigs, raising the possibility of growing human organs inside animals.
The research involved the creation of human-pig chimeric embryos containing a combination 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 had grown a solid humanized organ inside a other animal.
“Rat organs have been produced in mice, and mouse organs have been produced in rats, but previous attempts to culture human organs in pigs have been unsuccessful,” said the lead author. Liangxue Lai, from Guangzhou Institute of Biomedicine and Health, Chinese Academy. of Science 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 weren’t fully human as they comprised vascular and nervous systems made mostly of pig cells, meaning they couldn’t be used for transplantation in their current form. It is unclear whether the challenge of making a fully human organ would be feasible with current genetic engineering techniques.
Professor Dusko Ilic, a stem cell researcher at King’s College London, who was not involved in the research, called the work pioneering but said no clinical application would occur in the near future. “As the authors have admitted, the challenges are many,” he said. “Will this approach prove to be the ultimate solution? Only time holds the answer.
Apart 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 humanized brain is a serious ethical concern for research involving hybrid embryos and one of the reasons for the strict legal restrictions imposed on research in many countries.
In the UK, the introduction of human embryo cells into animal embryos is permitted, but the embryos cannot be implanted into a mother animal for further development.
Previous attempts to create human-pig hybrids have failed because porcine cells tend to outcompete human cells during development, meaning the resulting chimera is almost entirely porcine. The latest work, published in Cell Stem Cell, overcame this problem by genetically modifying a single-celled 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 embedded in the pig embryo.
After being cultured in the laboratory, the chimeric embryos were transferred to 13 surrogate sows. After 25 or 28 days, the gestation was terminated and the embryos were extracted and evaluated. 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 have been found in the brain and spinal cord.
“We found that if you create a niche in the pig embryo, human cells naturally enter these spaces,” said Professor Zhen Dai of the Guangzhou Institute of Biomedicine and Health, another lead author.
Scientists said it would likely take many years to be able to incubate a fully human kidney inside a pig. “We would probably need to design the pigs in a much more complex way, which would also bring additional challenges,” said Miguel Esteban, also from the Guangzhou institute and lead author.
A major challenge would be to allow human nerves and vasculature to grow within the target organ without nerve cells growing into the central nervous system, which could lead to a humanized brain. “Even in theory, it’s not clear exactly how to do it,” Ilic said.
theguardian