Bioreactor That Regrows Frog Body Parts Could Take Us Closer To Human Regeneration

An Xenopus laevis frog swimming in a tank, pre-amputation. Celia Herrera-Rincon/Tufts University

If you were cruel enough to slice off the leg of a newt, it would “miraculously” grow back to its original form, more or less. In fact, a select few tailed amphibians can even regenerate whole limbs, tails, jaws, eyes, and some internal structures.

Imagine the biomedical breakthrough if humans managed to harness the power of this nifty little trick. While that dream is still some way off, a new study has shown how we can kickstart the limb regeneration of African clawed frogs (Xenopus laevis) by plonking them in a bioreactor, a tiny box filled with a soup of hormones and electroceuticals attached directly to the wound following amputation. The success of the experiment is also leading scientists to think that perhaps full limb regeneration is possible in mammals too.

"At best, adult frogs normally grow back only a featureless, thin, cartilaginous spike," senior author Michael Levin, a developmental biologist at the Allen Discovery Center at Tufts University, explained in a statement. "Our procedure induced a regenerative response they normally never have, which resulted in bigger, more structured appendages. The bioreactor device triggered very complex downstream outcomes that bioengineers cannot yet micromanage directly."

As reported in the journal Cell Reports, scientists placed a gel laced with hydrating silk proteins that promote healing and regeneration and the hormone progesterone inside the 3D-printed bioreactor. Although progesterone is perhaps most commonly associated with menstrual cycles and pregnancy, it can also be used to promote nerve, blood vessel, and bone tissue repair.

“Maybe reproduction, brain processing, and regeneration are closer than we think,” added first author and neuroscientist Celia Herrera-Rincon.

The legless frogs were only left in the bioreactor for 24 hours, however, over the next 9.5 months, the frogs managed to grow a new limb with well-organized nerve fibers and blood vessels, which they could use to swim and paddle. Although it didn’t feature a fully formed foot, it was way closer to a fully formed limb than unaided regeneration could create.

"The bioreactor device created a supportive environment for the wound where the tissue could grow as it did during embryogenesis," said Levin. "A very brief application of bioreactor and its payload triggered months of tissue growth and patterning."

Many animals that are capable of effective regeneration are amphibians, namely newts or salamanders, or reptiles, such as lizards, which can regrow their tail if it has been pecked off by a bird. It’s been suggested that mice might be able to regenerate amputated fingertips under certain circumstances, but the wear and tear of walking on limbs means regeneration is hard. So, next up, the researchers hope to replicate their bioreactor experiment in mammals.

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