New Treatment Helps Frogs Regenerate Limbs With Functioning Nerves in Just 18 Months

The world is connected by our bodies. When people lose a part of their body, they feel like they have lost a part of themselves.

Their sense of personal loss is justified because unlike salamanders or comic book characters, limb loss is permanent and irreversible.

Is it?

While there have been advances in technology to replace lost limbs, they cannot yet restore a sense of touch, reduce the sensation of phantom pains or match the capabilities of natural limbs. Without reconstructing the limb itself, a person won't be able to feel the warmth of the sun or the touch of a loved one.

We are researchers in the fields of biology and engineering.

A recent study in the journal Science Advances shows that just 24 hours of treatment can regenerate fully functional and touch-sensitive limbs.

Kickstarting regeneration

Cells that will eventually become limbs and organs arrange themselves into precise structures using a set of chemical, biomechanical and electrical signals.

We thought it would be easier to ask cells to repeat what they did before. We looked for ways to build the signal for cells at the site of a wound.

One of the biggest challenges in creating an environment that encourages the body to regenerate is figuring out how to do that.

While scars help protect injured tissue from further damage, they also change the cellular environment in ways that prevent regeneration.

The axolotl has mastered regeneration without scar formation. In early human development, the amniotic sac provides an environment that can facilitate regeneration.

We believed that a similar environment could allow the body to reestablish itself after an injury.

The idea was to create an isolated chamber for regeneration by blocking signals that would cause the body to develop scars or other processes. The device was loaded with a cocktail of drugs involved in normal animal development.

African clawed frog is a species used in animal research which does not regenerate limbs in adulthood.

The device was attached to a leg stump for 24 hours. The site of the lost limb changed over time after we removed the device.

We were amazed to find that the frog's legs were regenerated over the course of 18 months, including fingerlike projections with significant nerve, bone, and blood vessel regrowth.

The limbs responded to light pressure and allowed the frog to return to normal swimming behavior.

Frogs that were given the device but not the drug cocktail had limited limb regrowth.

Frogs that weren't treated with the device or the drug cocktail didn't regrowth their limbs, leaving their stumps functionally impaired.

The limbs of the frog that were treated with the device were not perfect. Sometimes bones were fragmented. The incompleteness of the new limb tells us that other signals may be missing, and that many aspects of the treatment can still be improved.

Adding these signals to the drug treatment could potentially reverse limb loss in the future.

One of the leading causes of death and disability in the US is traumatic injury. The most frequent source of lifelong disability is limb loss from injury.

These traumatic injuries can be caused by automobile accidents, athletic injury, side effects of diabetes and even battlefield injuries.

decoding and awakening signals that allow the body to regenerate parts of itself is a new frontier in medical science.

After a heart attack or stroke, regenerating heart tissue can extend life and increase its quality. Our treatment is not ready to be used in humans, and we only know that it works when applied immediately after an injury.

Patients may not have to wait for scientists to understand how complex organs are constructed before they can be treated if they understand the signals that allow cells to regenerate.

Making a person whole again is more than just replacing their limb. They need to restore their sense of touch and function. New approaches are starting to identify how that may be possible.

Professors of Biology, Tufts University, David Kaplan, and Nirosha Murugan are also Assistant Professors of Biology.

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