Dr. Jun Wu and associates of the Salk Institute have published a report on the successful growth of human stem cells in pig embryos. The project may have implications for transplant organ development, although research is still in its early stages.
A chimera is an animal with cells from multiple organisms. The institute first created mouse-rat chimeras while testing a genetic editing technology called CRISPR-cas9. Due to the physiological differences between rats and humans, the researchers eventually moved on to pigs because of their physical similarity to humans.
Pig-human chimeras have been developed, but the dispersal of the introduced human stem cells around a chimera’s body creates organs containing cells from both species. The human immune system would reject organs with too many pig cells.
The question then becomes: how do scientists concentrate the stem cells to create a human organ? The answer is the CRISPR-cas9 system, a technology which geneticists use to “turn off” specific genes. Although the issue of spread out cells remained in the later pig-human chimeras; they solved it in rat-mouse experiments. The scientists could grow a mouse with a specific organ made almost completely of rat cells.
Cas9 is an enzyme in cells which acts as a defense mechanism. It deactivates harmful DNA injected into the cell by a virus. Scientists modify cas9 to bind with a gene of their choosing. This allows them to deactivate specific genes the same way natural cas9 deactivates virus DNA.
In the case of Salk Institute’s chimeras; the deactivated gene would normally be the instructions for the development of the specified organ. Scientists found that with rats, an introduction of stem cells from a foreign species will replace the “deleted” organ with one made of the foreign species’ cells.
In mouse-rat chimera experiments, scientists have used the CRISPR-cas9 system to create mice with hearts, pancreas and eyes developed from rat stem cells.
This method was less efficient when trying to grow predominantly human organs in a pig. The institute used a fluorescent marker that lights up human cells integrated into the pig embryos. This allowed them to measure the degree of chimerism achieved.
Results of the pig-human chimera attempts suggest that the injection of human stem cells often stunts the embryo’s growth. Half of the 186 survived embryos injected with human stem cells had stunted growth. 67 of the embryos showed fluorescence indicating that human cells had been successfully integrated. 17 of these fluorescent positive embryos were normal sized and these grew less human cells than the 50 stunted embryos.The researchers included other indicators and tests to strengthen their findings of human cell integration.
Although science is far from creating usable organs this way, this study is also a step towards more accurate animal-testing models. Pig-human chimeras could also provide a new platform to study human pathology.