Lab-made tadpole cyclopes could help with human organ transplants

Lab-made tadpole cyclopes could help with human organ transplants

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At first blush, a blind tadpole that’s had an eyeball grafted onto its tail sounds like a creature from a fairy tale — the Cyclops’ tadpole cousin. But these tadpoles exist (scientists made them!) and they could actually see through the grafted eyes after being treated with migraine medication. In fact, the feat is even more astonishing than that: the eyes didn’t connect directly to the brain, as eyes ordinarily do; they connected to the spinal cord instead. The results suggest that the tested medication, or other similar drugs, could one day help patients better integrate transplanted organs into their own bodies.

For a transplanted tissue or organ to fully operate in a new body, its nerves have to wire into the recipient’s nervous system. That’s difficult, says lead author Michael Levin, a professor of biology and director of the Allen Discovery Center at Tufts and the Tufts Center for Regenerative and Developmental Biology. So his team began testing methods to help make that connection. A migraine drug can help the transplanted eye wire into the recipient’s nervous system — allowing blind tadpoles to see, according to the study published in the journal npj Regenerative Medicine. “It really helps the vision,” says Levin. “It makes the animal see better.”

Levin and his team engineered frog embryos to grow into blind tadpoles. They then grafted an eye onto their tails, and dosed them with zolmitriptan, a drug that activates serotonin receptors associated with neural growth. In experiments, the researchers saw that the tadpoles could see from their new eyes: they could detect colors and follow rotating patterns. That’s because the zolmitriptan boosted neural growth, creating new connections between the transplanted eyes and the tadpoles’ nervous systems. That was possible even though the eyes were not directly connected to the animals’ brains — but indirectly, through the tadpoles’ spinal cords. The tadpoles’ brains had no problem recognizing signals coming from an eye grafted in a completely foreign place: their tails instead of their heads. “That’s the interesting part,” says Levin.

The short-term implications of the study have to do with organ transplantation, Levin says. Similar neurotransmitter drugs could be used in the future to help boost the neural growth of all kinds of organs — whether they’re taken from donors, grown in labs from stem cells, or grown inside human-pig chimeras. “Our study is one of the very first examples of repurposing those kinds of drugs for applications in regenerative medicine,” Levin says.

The longer-term implications of the study, as Levin talks about them, sound very sci-fi. The study shows that the brain is incredibly adaptable to physical changes. In the far future, this technology could be used for sensory or motor augmentation. This might be the first step toward modifying the human body for extreme environments. “You [could] have people living at the bottom of the ocean or maybe they’re undergoing space travel,” Levin says. “In the coming century, the human body is going to undergo all kinds of changes. And it’s really important to know that, when that happens, the cognitive and behavioral programs of the brain are not going to just fall apart and be useless.”

Before we get to that point though, today’s study needs to be replicated in mammals. Levin wants to understand whether certain transplanted organs respond better to the drug, and find out how to control how the nerves develop. It’s also important to understand whether the brain plasticity observed in this study goes beyond eyes and applies to other senses, so Levin is now working on tadpoles with out-of-place nostrils and frogs with extra legs.

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