The embryos, which were less than 0.001 percent human, could provide insight into early development and are a first step towards creating animals that could grow human organs for transplantation.
The team aimed to create human–animal chimeras using pig and cow embryos as the size of these animals' organs is relatively close to those of humans. Although cow embryos proved to be too expensive and complex to use, 2075 early-stage pig embryos were injected with intermediate-stage human pluripotent stem cells. These were found to be the most successful type of stem cell to produce the chimeras.
The embryos were then implanted into sows – 185 embryos continued to develop, resulting in human–pig chimeras comprising approximately of one human cell per 10,000 pig cells.
Although the rate of success was low, Professor Izpisua Belmonte considered this a positive sign as ethical concerns could arise in particular if human cells contribute to brain tissue.
No embryonic development was allowed to proceed past four weeks.
'One possibility is to let these animals be born, but that is not something we should allow to happen at this point,' said Professor Izpisua Belmonte. 'Not everything that science can do we should do, we are not living in a niche in lab, we live with other people – and society needs to decide what can be done.'
Previous chimeras were typically created by inserting human cells at a later stage of development. The researchers say their work shows human cells can contribute to the development of a pig embryo. Next they plan to use CRISPR/Cas9 to edit the pig genome in order to improve the development of the human cells.
'The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that,' said Professor Izpisua Belmonte. 'This is an important first step.'
Professor Bruce Whitelaw of the University of Edinburgh, who was not involved in the study, called it 'an exciting publication' which 'paves the way for significant advances in our understanding of development in the embryo and hints towards future novel biotech applications'. Reflecting on the production of the first live rat–mouse chimeras, he said, 'The 10 years between these two studies is a testament of how difficult it has been to achieve the human–pig result.'
In the study, published in Cell, the team also reported the production of several rat–mouse chimeras using CRISPR/Cas9 genome editing. Another study in Nature this week also reports creation of rat–mouse chimeras, producing functional mouse pancreases in rats (see BioNews 886).