A team of bioengineers at Colossal Biosciences, a de-extinction company based in Dallas, Texas, has announced that they have successfully created induced pluripotent stem cells (iPSCs) from elephant skin cells. This is a major technical achievement in the company’s ambitious project to engineer elephants with woolly mammoth traits, such as shaggy hair and extra fat.
What are iPSCs and why are they important?
iPSCs are cells that have been reprogrammed to act like embryonic cells, which can differentiate into any of the animal’s cell types. They are key to Colossal Biosciences’ plans to create herds of Asian elephants, the closest living relatives of extinct woolly mammoths, that have been genetically edited to have mammoth-like features. The company hopes that these animals could be released into the wild in places like Siberia, where they could perform the same ecological role that was once played by woolly mammoths.
How did the team create iPSCs from elephant skin cells?
The team, led by Eriona Hysolli, Colossal Biosciences’ head of biological sciences, faced many challenges in creating iPSCs from elephant skin cells. Elephants have unique biology that makes it much more difficult to create iPSCs using their cells than those of other species, such as white rhinoceroses and drills, which have been successfully engineered to become iPSCs by other researchers.
To overcome this obstacle, the team used a different approach involving treating the elephant skin cells with chemicals used to engineer mouse and human cells. They also added so-called Yamanaka factors and changed genes that were responsible for the production of TP53, a protein that regulates cell growth and death. The result was four lines of elephant iPSCs, which looked and behaved like other iPSCs created from other animals.
What are the next steps and challenges?
The team is still in the process of writing a paper describing their work and plans to post it on the bioRxiv preprint server soon. They are also working on editing the elephant iPSCs to introduce mammoth genes, such as those for hair growth and cold tolerance. However, there are still many technical hurdles to overcome before the team can achieve their ultimate goal of creating a living animal with mammoth traits.
One of the biggest challenges is finding a way to turn the iPSCs into viable embryos that can be implanted into an elephant’s womb. This would require creating artificial structures called blastocysts, which are hollow balls of cells that form early in development. So far, no one has been able to create blastocysts from iPSCs of any species.
Another challenge is finding suitable surrogate mothers for the embryos. Asian elephants are endangered and there are ethical and practical issues involved in using them for experimental purposes. The team may need to find alternative hosts, such as African elephants or even artificial wombs.
Finally, there are ecological and social implications of bringing back an extinct animal or creating a new one. The team will need to consider how these animals would interact with their environment and other species, as well as how they would be accepted by local communities and governments.
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