- Scientists got amputated frogs to grow leglike limbs using a growth-stimulating drug cocktail.
- Stem cell transplants and rerouted nerves have previously induced limb regrowth in lab animals.
- Regrowing human limbs is a much bigger challenge, but some researchers think they'll live to see it.
Like humans, African clawed frogs can't regrow missing limbs — yet. Scientists have gotten frogs with amputated legs to grow new, leglike appendages in the laboratory, and may be able to help humans regrow limbs in your lifetime.
Researchers at Tufts University applied a five-drug cocktail to the stumps where the frogs' legs had been amputated. For 24 hours they let the stumps soak in the treatment, which was designed to instruct cells to multiply.
Within 18 months, the frogs had grown leglike limbs from their amputations and were using them to swim. Though their new appendages had no toenails or webbing between the toes, the legs were fully functional, complete with new skin, vasculature, nerves, and most of the necessary bone.
The drug cocktail worked because it used compounds that are part of normal development — like growth hormone, anti-inflammatories, and collagen inhibitors to prevent scarring — Tufts researcher Nirosha Murugan told Insider. She led the new study, which was published in the journal Science Advances on Thursday.
Scientists are decades away from regrowing missing human limbs, but Murugan, age 31, thinks she'll live to see it.
"The biomedical engineering aspect is actually making these new advancements to kind of understand and fix biology. And I think that integration is going to make this happen in our lifetime," she said.
Others are less optimistic about living to see a human limb regrown.
"Provided I live another 45 years, which would make me 90, I don't think we will be able to regenerate an entire adult human limb," Ashley Seifert, who heads a regeneration lab at the University of Kentucky, told Insider in an email.
Kelly Tseng, who leads regeneration research at the University of Nevada, declined to make any predictions about human-limb regrowth in her lifetime.
"Regeneration has been studied for over 300 years. It's one of the oldest topics in biology and it's a difficult topic to study," she told Insider.
If regenerative therapies ever work for humans, they might help regrow organs. Regrowing limbs — even if they're not exactly like the originals — could help amputees with phantom-limb pain, a condition in which nerves at the amputation site continue sending pain signals to the brain.
Regrowing mammal limbs is a bigger challenge than frog legs
Humans do some regrowing already. Human livers can grow back after 90% of the organ has been removed. Young children can regrow their fingertips. The top layer of our skin regularly regenerates.
Generally, though, mammals cover their wounds with scar tissue, which prevents the body from reproducing damaged or lost tissues.
Scientists don't fully understand what makes a wound heal by scarring versus regeneration. Investigating those processes is critical for learning to induce regrowth in human organs and limbs, according to Seifert. That's what he's doing in his own lab with the spiny mouse, which can regrow its ears after a large hole has been punched into them.
Stem cells, nerves, and drugs have helped regrow lab-animal limbs
Seifert called the new frog legs a "marginal success" and pointed to the work of Marcus Singer, a zoologist who partially regenerated frog limbs in the 1950s by rerouting the sciatic nerve. In 2013, researchers at the University of Minnesota produced frog limbs with toe-like digits, similar to the ones in Murugan's study, by transplanting stem cells to the amputation site.
Other labs are still studying stem-cell therapy for regrowing limbs. Still others are adding genes or otherwise manipulating cells' genome to encourage growth.
"As researchers, we have our own favorite approach or, you know, what we think might be a better method," Tseng, who studies stem cells' regenerative capacites, said. "But there could be multiple ways to get to the same goal."
Researchers at Tulane University have even had some success regrowing mouse limbs. In a 2012 study, they covered mouse amputation wounds with a patch containing a protein that stimulates bone development. The mice grew new bones, but like Murugan's frogs, their new limbs did not form joints.
Murugan's team used a similar method. They applied a silk-based gel containing growth-stimulating medicine to the amputation site via a silicone cap called BioDome.
Two of Murugan's colleagues who worked on the study, Michael Levin and David Kaplan, co-founded a company to develop the BioDome technology for clinical application, The Wall Street Journal reported.
Seifert and Tseng both said that they like this approach — applying drugs that encourage existing cells to grow — because it doesn't involve manipulating genes or introducing new stem cells. That ease could give this method an edge for potential medical applications.
Murugan's team is moving on to mice. Levin used the BioDome on mice with amputated digits before, and it didn't regrow the missing toes — but now they have a new drug cocktail to apply.
Similar to stem cells, researchers using the drug-cocktail method must avoid triggering the patient's immune system, which could accidentally prompt scarring.
"Will we one day be able to regenerate a human digit or even a limb? Probably, but how long we need to wait is impossible to predict," Seifert said. "This and comparative studies will help us understand how and why regeneration fails in some contexts and succeeds in others."