Producing these potentially disease-curing cells within another living organism, in vivo, is critical to ensure they develop as they would in a human body. Cells produced in a dish, in vitro, usually do not behave in the same way as cells in vivo. However, high yields have been difficult to achieve in the past due to the varied timing between species' developmental clocks.
The human stem cells are in a more developmentally advanced 'primed' state compared to 'naïve' mouse embryonic stem cells, and this discrepancy between the cells' different developmental stages is thought to be responsible for the cell death which occurs when the two are combined. 'You need to basically push the human cells back' explained Professor Feng.
The team, based at the University of Buffalo, inhibited a molecule called mTOR kinase for three hours. This shocked the 'primed' human cells back to their 'naïve' state. When added to a less developed naïve mouse embryo, these human stem cells speed up their development to match their host. 'The injected human stem cells now develop at the much more rapid pace of the mouse embryo, supporting the generation of millions of mature human cells in 17 days,' said Professor Feng. The human stem cells aided the formation of many tissues in the developing mouse embryo, such as human liver, eye and red blood cells.
The researchers' primary reason for conducting this research is to find ways to grow organs for people who need transplants. However, this research, published in Science Advances, could have multiple applications, including the creation of mouse models that are more like humans, or revealing how a single cell develops into an entire organism.
Dr Pablo Ross who was not involved in the study, but specialises in animal reproduction at the University of California, Davis said, 'This is great if we want to generate human organs in animals'. The idea here would be to modify the genome of larger animals, such as a sheep or pig, so they cannot develop certain organs. Then, using a similar approach, human stem cells could develop within these animals to generate human-like organs for transplants.
However, Professor Feng raised concerns that the product may not be similar enough to human organs for this purpose. Instead, he suggested his system could lead to the discovery of methods that would allow human organs to grow for transplantation without the need for a host, such as in an incubator.
The ethical implications will need to be discussed to determine what can be achieved in this area.