Feb. 2, 2022 -- Could missing human limbs be regrown? That’s a possibility scientists are now considering after regenerating frogs’ legs for the first time.
Scientists say they have been able to help frogs regenerate limbs using a five-drug combination. Though other animals -- including salamanders, starfish, zebrafish, lizards, and crabs -- can do that on their own, frogs can’t.
The successes of a team of researchers at Tufts and Harvard universities in Boston are raising hopes that one day, human limbs or organs can be regrown. The potential is tremendous, the researchers report in Science Advances.
Over the next 30 years, more than 3.6 million people a year in the United States alone are expected to lose limbs from diabetes, military combat, trauma, and peripheral artery disease, according to the paper's authors. Prosthetics offer only limited help with mobility.
While there have been many scientific advances in the area, scientists have not been able to recover tissue loss or reverse it.
The researchers combined five drugs to help adult frogs regrow their back legs. The drugs were put into gel in a wearable dome called a BioDome. The dome was sealed over the frog's stump for 24 hours after amputation. The new limb growth occurred over the next 18 months.
The scientists report in a news release that they used the five-drug method after their previous work using a single drug, progesterone, with the BioDome. In the single-drug method, the limb grew as a spike and didn't have the function of the limbs in the current study.
Each of the five drugs had a different role, including easing inflammation, stopping collagen production to avoid scarring, and encouraging the growth of nerve fibers, blood vessels, and muscle.
"The new limbs had bone structure extended with features similar to a natural limb's bone structure, a richer complement of internal tissues (including neurons), and several ‘toes’ grew from the end of the limb, although without the support of underlying bone," they reported.
Nirosha Murugan, PhD, a research affiliate at the Allen Discovery Center at Tufts and first author of the paper, says the completeness of the regrown limb was exciting.
"The fact that it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests that frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action," she says.
Activating the pathways could allow the limb to take on the process of growth and organization of tissue similar to the way that happens in an embryo, rather than requiring ongoing therapy over the months it takes to grow the limb, the scientists say.
After regrowth in many of the frogs, the new limbs were able to respond to touch and were ready for use in swimming and moving.
So what’s the next step for the research?
"We'll be testing how this treatment could apply to mammals," said author Michael Levin, PhD, a professor of biology at the Tufts School of Arts & Sciences and director of the Tufts Allen Discovery Center.