In a world first, scientists have grown human kidneys inside pig embryos – a breakthrough hailed as a major step towards the unlimited production of organs suitable for life-saving transplants.
The part-human, part-pig embryos – known as “chimeras” – were implanted in surrogate sows and allowed to develop for a full trimester, lasting 28 days, before the pregnancies were terminated.
Upon extracting the embryos, the researchers found that the kidneys had up to 60 per cent human cells, were structurally normal, and were in the second stage of development.
It marks the first time that scientists have been able to grow a solid human organ inside another species, although similar methods have previously generated human tissues such as blood and muscle, according to the team based at the Beijing-sponsored Guangzhou Institutes of Biomedicine and Health.
“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 senior author Liangxue Lai. ““Our approach improves the integration of human cells into recipient tissues and allows us to grow human organs in pigs.”
Scientists have previously struggled to integrate human stem cells into pig embryos, because pig cells and human cells end up competing with each other.
To overcome this problem, the researchers used gene editing technology to remove two genes from pig embryos – thereby creating a genetic “niche” or “void”, and enabling the resulting embryo to grow human kidneys.
“We found that if you create a niche in the pig embryo, then the human cells naturally go into these spaces,” said senior author Zhen Dai.
The researchers then engineered human stem cells – which have the potential to become any type of tissue in the body – to make them more amenable to developing in the pig embryo.
The embryos were initially grown in conditions in the lab that catered to both pig and human cells and their different needs, before being implanted in surrogate sows.
In total, the researchers transferred 1,820 embryos to 13 surrogate mothers, whose pregnancies were terminated within 28 days. Ethical guidelines advise against letting chimeras develop completely.
According to the results published in the journal Cell Press, the team found that, at 25 to 28 days, the the kidneys were structurally normal for their stage, and had formed tubules and buds of cells that would eventually become ureters, connecting the kidney to the bladder.
With up to 60 per cent human cells, analysis showed that these were mostly localised to the kidneys, while the rest of the embryo was comprised of pig cells.
In the future, the team wants to allow the kidneys to develop for a longer duration – and are also working to generate other human organs in pigs, including the heart and pancreas.
While their aim is ultimately to use the technology for human organ transplantation, they said that far more work lies ahead.
“We would probably need to engineer the pigs in a much more complex way and that also brings some additional challenges,” said Miguel A Esteban, also of Guangzhou Institutes of Biomedicine and Health.
“Before we get to that late state of making organs that can be on the shelf for clinical practice, this method provides a window for studying human development. You can trace the human cells you’re injecting and manipulate them so that you can study diseases and how cell lineages are formed.”
Commenting on the research, Dusko Ilic, professor of stem cell sciences at King’s College London, said: “The paper describes pioneering steps in a new approach to organ bioengineering using pigs as incubators for growing and cultivating human organs.
“As the authors admitted, there are plenty of challenges. Will this approach prove to be the ultimate solution? Only time holds the answer. Nevertheless, this captivating strategy warrants further exploration.”
Rafael Matesanz, creator and founder of Spain’s National Transplant Organisation, added: “The next steps will be to allow embryos to grow longer and to start doing the same with other organs and tissues, although the kidney is undoubtedly the most sought-after organ for transplantation.
“The authors themselves acknowledge that the clinical use of this technology is years away but it is a major achievement on the road to unlimited organ production for transplantation.”
Additional reporting by PA