Chimeras have cells from two different organisms growing in the same animal. You might see some wild headlines about these findings, but chimeras are not uncommon in the modern laboratory; making a transgenic mouse utilizes chimeras as an integral part of the process. Scientists have also used chimeras as a way to grow organs from one animal in another, which could be a way to generate much needed transplant organs for use in human patients. Scientists at the Salk Institute have now reported advancements in technologies that fuse stem cells from one species into the developing embryo of another. Check out their video below to learn more.
In their work, published in Cell, the researchers have coupled stem cell techniques with the CRISPR/Cas9 gene editing technology to successfully grow a rat heart, eyes and pancreas in developing mice. This demonstrates that it’s possible to grow a usable organ for one animal in an entirely different species. Additionally, they showed that human cells and tissues could be generated in pig and cattle embryos at the early stages of development. This work brings us forward in the search for a way to grow human organs in donor animals that are of a similar size to humans and have roughly comparable anatomical functions.
“Our findings may offer hope for advancing science and medicine by providing an unprecedented ability to study early embryo development and organ formation, as well as a potential new avenue for medical therapies,” said a senior author of this study, Salk Professor Juan Carlos Izpisua Belmonte. “We have shown that a precisely targeted technology can allow an organism from one species to produce a specific organ composed of cells from another species. This provides us with an important tool for studying species evolution, biology and disease, and may lead ultimately to the ability to grow human organs for transplant.”
Using CRISPR/Cas9 on mouse embryos, the scientists silenced a gene responsible for creating a pancreas. After putting rat stem cells that harbored a normal pancreas gene into those mouse embryos, the mice then began to grow a rat pancreas. The team then tried their hands at other organs. They were even able to coax the mice to create a gallbladder – an organ that mice normally don’t even have.
“Our rodent experiments reveal a profound secret, that a developing mouse was able to unlock a gallbladder developmental program in rat cells that is normally suppressed during rat development,” commented the lead author of this and previous work, Jun Wu, a Salk staff scientist. “This highlights the importance of the host environment in controlling organ development and evolutionary speciation.” The scientists think this shows that it’s possible to generate human transplant organs in other species.
“Each mouse was healthy and had a normal lifespan, which indicated that the development proceeded properly,” said Wu. Because rodents clearly aren’t a good match for the size of human organs, the researchers then looked to pigs. After optimizing the stem cells, they were inserted into pig embryos that were subsequently implanted in sows. After four weeks, the scientists assayed the results.
While the success rate was lower than what is seen in rodents, the investigators saw that some human cells were indeed growing into the precursors for the desired tissues. This research is still laying the foundations for the myriad potential applications of this idea, but it’s a step in the right direction.
“Of course, the ultimate goal of chimeric research is to learn whether we can use stem-cell and gene-editing technologies to generate genetically-matched human tissues and organs, and we are very optimistic that continued work will lead to eventual success,” says Izpisua Belmonte. “But in the process we are gaining a better understanding of species evolution as well as human embryogenesis and disease that is difficult to get in other ways."
Sources: Salk Institute, Cell