Researchers have successfully regrowed limbs on frogs. They want to do the same with humans

Most animals have fairly good wound healing abilities, but when a limb is lost, only a select few are able to regrow it. The rest, including humans, can do little to repair such injuries. But as a new study shows, with the right treatments, our bodies can be attacked and “persuaded” to regrow lost limbs. Although the study focused on frogs, which are clearly very different from humans, the proof-of-concept study suggests that this approach could work in many animals, including humans.

African hoofed frog (Xenopus laevis). Image via Wiki Commons.

Limb reconstruction is a new frontier in biomedical science. It’s something we’ve long considered beyond the realm of possibility, limited to superheroes and myths, but research is bringing it closer and closer to reality.

While many things distinguish humans from frogs, neither we nor them can regenerate limbs. So, researchers at Tufts University and Harvard University’s Wyss Institute used frogs (specifically, African clawed frogs or Xenopus laevis) as a proof of concept. X. laevis To be commonly used in research because it’s easy to handle, spawns year-round, and for a model organism, share a close evolution relationship with humans.

The researchers triggered the regrowth of a lost leg using a cocktail of five drugs that they administered in a wearable silicone bioreactor dome to seal the drugs on stump in just 24 hours. Once the treatment was performed, regeneration was initiated, and over a period of 18 months, the frogs had grown back a nearly fully functional leg.

“It was exciting to see that the drugs we chose helped create a nearly complete genus,” said Nirosha Murugan, research associate at the Allen Discovery Center in Tufts and first author of the paper. . “The fact that only a brief period of drug exposure is needed to initiate a months-long regeneration process suggests that frogs and perhaps other animals that may have inactive regenerative abilities can be stimulated. active.”

The experiment was repeated on dozens of frogs, and although not all of them regrow their limbs, most did – including bone tissue and even toe-like structures at the end of their legs. limbs (although they are not supported by bones). It’s no panacea, and the treatment isn’t perfect, but the drug cocktail delivered through a wearable bioreactor is indeed capable of regrowing limbs.

Soft tissue regeneration. The MDT group (bottom) represents a five-drug cocktail of treatments. Image credit: Murugan et al (2022).

Researchers have essentially hijacked the biological pathways that enable tissue growth and organization – just like in an embryo. This is why the treatment is only applied once, over the course of a day; whereas, other approaches involve multiple interventions throughout the process.

The remarkable complexity of functional limbs suggests that the fastest path to this goal may lie in the activation of self-limiting modules of the process, the researchers write in the study. organogenesis, not the ongoing micromanagement of elongation at the cellular and molecular levels”. “We did this through brief exposure of amputation wounds to a wearable bioreactor containing five selective biochemical factors.”

The first stage is the formation of a stem cell mass at the end of the stump, which is then used to gradually regenerate the limb. It is essential that this structure be covered by the dome as quickly as possible after amputation to ensure its protection and activation. This treatment would ideally be applied immediately after amputation.

“Mammals and other regenerative animals will be injured by exposure to air or contact with the ground, and they can die,” said David Kaplan, Stern Family Professor of Engineering at Tufts et al. days to weeks to close the scar tissue. author of the study. “Using the BioDome cap for the first 24 hours helps to mimic the amniotic fluid-like environment, along with the right medications, allowing the rebuilding to take place without the intervention of scar tissue.”

At first, the researchers tried using a protective dome with a single drug, progesterone. Progesterone is a steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. This alone triggered several developmental limbs, but the resulting limb was essentially a non-functional limb. Each of the remaining four drugs performs a different role, from reducing inflammation and preventing scar tissue formation to promoting the growth of new nerves, blood vessels and muscles. It is the combination of all of these together that results in a well-functioning chi.

The researchers note that while the limbs are not 100% identical to “normal” limbs, they do have numerals, contours, and detailed skeletal and muscular features. Overall, the results indicate a successful “starter” of regenerative pathways

The plan now is to move on to mammal research. Despite the differences between frogs and mammals, the researchers say the biggest difference lies in the “early events of wound healing” – if these early processes can be understood and scaling, there is no clear reason why this cannot apply to mammals, and ultimately to humans.

The goal of activating latent tissue-building processes for limb regrowth in humans can be achieved by identifying and exploiting principles observed in organisms, the researchers conclude. highly regenerative,” the researchers concluded.

Research published, published in the magazine Scientific advance. Researchers have successfully regrowed limbs on frogs. They want to do the same with humans

James Brien

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