Hundreds of mouse pups with partial rat brains have been born from embryos made from a mix of mouse and rat cells, marking the first time that the brain of one species has been grown in another from the embryonic stage.
Over the past decade, scientists have been experimenting with growing human organs inside other animals to address the worldwide organ donor shortage. Most recently, at Guangzhou Institutes of Biomedicine and Health in China and his colleagues partially grew human kidneys in pigs by synthesising embryos from human and pig cells, then letting them develop inside surrogate sows for up to 28 days.
The embryos were terminated after this short time because of fears they might become pigs with human-like brains if they were allowed to continue to develop.
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To explore whether this is a realistic possibility, at the University of Texas Southwestern Medical Center and his colleagues tried creating mice with rat brains from hybrid embryos.
First, they disabled a gene called Hesx1 in mouse embryos, which impaired their ability to grow their own forebrains 鈥� the largest part of the brain, which includes the left and right cerebral hemispheres. They then introduced rat stem cells into the embryos that could transform into rat brain cells in place of the missing mouse ones.
The hybrid embryos were implanted in the uteruses of adult mice and allowed to develop to full term, resulting in the births of 417 pups.
The pups鈥� forebrains were composed of up to 60 per cent rat cells while the rest were mouse cells, and they appeared structurally and functionally similar to regular mouse forebrains. The animals also performed similarly to normal mouse pups in cognitive tests, including learning the way through a maze, and displayed typical weight gain and lifespans.
Brain tissue from people has previously been transplanted into rodents, but this marks the first time that the brain of one species has been grown in another from the embryonic stage.
Having forebrains composed of 60 per cent rat cells probably didn鈥檛 make noticeable differences to the mice because they have similar brains to rats to begin with, says Wu.
The study shows it is possible to at least partially grow rat brains in mice. However, it would be harder to grow human brains in pigs or other animals with larger anatomical and physiological differences, says Wu. Even with closely related mice and rats, as well as deliberate genetic engineering, it was only possible to partially grow the brain of one species in another, he says. 鈥淚 think it would be hard to generate a human brain in another animal even if you wanted to.鈥�
This is reassuring because it suggests that attempts to grow human kidneys and other transplant organs in pigs are unlikely to create pigs with human-like brains, says Wu, although he still believes we need to proceed cautiously and conduct more research.
bioRxiv
