Scientists have made a stem cell breakthrough in elephants, which could mean researchers are one step closer to bringing back long-extinct woolly mammoths, the de-extinction company Colossal Biosciences has announced.
In a statement shared with Live Science, Colossal's Woolly Mammoth team says it has successfully derived induced pluripotent stem cells (iPSCs) from Asian elephants (Elephas maximus). iPSCs are cells that have been reprogrammed so they can give rise to any cell type in the body, meaning researchers will now be able to investigate the adaptations that differentiate woolly mammoths (Mammuthus primigenius) from their closest living relatives and test gene edits without having to take tissue from living animals.
"These cells definitely are a great benefit to our de-extinction work," Eriona Hysolli, the head of biological sciences and mammoth lead at Colossal Biosciences, told Live Science. What's crucial about them, Hysolli said, is that they can reveal the cellular and genetic processes behind features that helped woolly mammoths thrive in the Arctic. These features include shaggy hair, curved tusks, fat deposits and a dome-shaped cranium.
iPSCs also open a path to creating elephant sperm and egg cells, which are essential for mammoth de-extinction, in the lab. With fewer than 52,000 Asian elephants left in the wild, according to WWF, harvesting cells from these animals would prove difficult and undesirable.
Previously, deriving elephant iPSCs proved challenging because these animals have a complex gene pathway not found in other species. The researchers overcame this by suppressing core genes called TP53 that regulate cell growth and prevent cells from duplicating indefinitely, Hysolli said.
"One of the things that we had to overcome for elephant cells is that they do have this expansive TP53 pathway," Hysolli said. "We had to suppress this pathway via two means in order to get these iPSCs, so we had to go through a multistep process in order to achieve them."
The breakthrough may also shed light on early development in elephants, which is currently considered the biggest hurdle to woolly mammoth de-extinction. If researchers succeed in creating a woolly mammoth embryo by fusing ancient mammoth DNA with elephant cells, they will need to implant this embryo into an elephant surrogate to complete a 22-month gestation period. "Elephant gestation is so long and complex, so really understanding the developmental biology aspect of elephant biology is so important," Hysolli said.
Engineering a woolly mammoth embryo no longer poses a huge challenge, Hysolli said, but birthing a healthy calf will take more time and work. The team is still researching alternative methods to generate elephant iPSCs and maturing the ones they have newly developed. The iPSCs breakthrough, which will be published on the preprint database bioRxiv, has yet to be peer-reviewed.
"There is more validation to be done, so until you do the experiment you can never be sure, but we think that the pluripotency potential [to differentiate into any cell type] is fully there," Hysolli said.
This is an important breakthrough and an essential step to create a woolly mammoth-like elephant, said Vincent Lynch, a developmental biologist and associate professor at the University at Buffalo in New York who was not involved in Colossal's work. "The goal, I think, is to turn these iPSCs into sperm and eggs, which would allow for in vitro fertilization and, eventually, surrogacy," Lynch told Live Science in an email. "Those methods are pretty challenging and haven’t been developed yet, but it is only a matter of time."
Reprogramming elephant cells into iPSCs has applications beyond woolly mammoth de-extinction, according to the statement. The technology could provide a boost to elephant conservation, for example, by enabling researchers to produce and fertilize reproductive cells artificially.
"We can derive gametes, so oogonia and spermatogonia-like cells, from these pluripotent stem cells," Hysolli said. "And that's crucial over the longer term, because they can really hold the key to saving species."
