Scientists have identified a new type of pluripotent cell that can divide and generate the three germ layers when injected into a developing mouse embryo, providing the first demonstration that human stem cells can begin a differentiation program inside mice.
The new type of cells, isolated from early mouse embryos and cell lines of both humans and monkeys, could help scientists build better models of human developmental disorders at an early stage and eventually be used for growing tissues and human organs in large animals for research or therapeutic purposes.
These cells are further differentiated than the previously isolated pluripotent cells and have more favourable characteristics for laboratory manipulations, such as high cloning efficiency, stable passage in culture and ease of genetic engineering. “All of these are advantages for applications in research and, potentially, scaling up for clinical applications,” said stem sell biologist George Daley from Harvard Medical School, who was not involved in the research.
The international team of scientists behind the new discovery sought to transplant the two known human stem cell types into mouse embryos in vitro. Thirty six hours after injecting a 7.5-day-old mouse embryo with the cells in three different regions, the researchers found that only the cells that were grafted into the tail integrated and differentiated into the correct cell layers, forming a chimaeric embryo – an organism with DNA of different origins. Because these cells seemed to prefer one part of the embryo, the researchers dubbed them region-selective pluripotent stem cells, or rsPSCs.
A closer analysis showed that the rsPSCs are capable of forming colonies from single cells and produce smaller teratomas – tumours that resemble embryos, including tissues from all three germ layers- when injected into mice.
“The high clonal efficiency was surprising, as was the data that these cells form smaller teratoma,” said Paul Knoepfler, a stem cell biologist at the University of California, Davis. “Anything that forms a smaller teratoma would have a potentially better safety profile for clinical applications,” he added.
The researchers also found that they could easily use DNA-cutting enzymes to edit the genomes of the new cells, which is usually hard to do in pluripotent cells grown in vitro.
In the future, gene editing could help scientists create animals with human organs, although this would probably prove to be very difficult due to the efforts required to prevent the host immune system from rejecting the organs that may be identified as foreign.
One of the researchers, Juan Carlos Izpisua Belmonte, a developmental biologist from the Salk Institute for Biological Studies in La Jolla, California, said this would also raise some hard ethical questions: “Of course, the ethical implications behind creating a human-animal chimera for the purpose of obtaining human tissues and organs to save lives of millions needs to be carefully evaluated.”
Results of the study have been published online on May 6 in the journal Nature.