▎ WuXi AppTec content team editor
For scientists in the field of regenerative medicine, finding a way to help regenerate limbs is one of their ultimate goals. Finding the secret of limb regeneration can help patients who have lost their limbs due to trauma and diabetes to regain their functional limbs. At present, many studies are focusing on some animals with regenerative abilities, trying to find some clues.
Animals such as salamanders, starfish and lizards have the ability to regenerate some limbs, while flatworms can even rebuild into a complete organism after being cut into small pieces, but humans are more likely to produce scar tissue to cover the wound after large areas of injury, rather than to regrow the original intact tissue.
▲ A floating toad on the surface of the water (Image: Wikipedia, CC BY-SA 4.0)
Recently, a joint team from Tufts University and Harvard University used a combination drug to make adult Xenopus that cannot regenerate limbs grow new legs, artificially creating a regenerative miracle, which also means that we are one step closer to the ultimate goal of regenerative medicine.
Their new study, published in Science Advances, focuses on a very specific point, the environment in which regenerated animals are often aquatic, and after these animals lose limbs, the stumps accumulate a large number of stem cells, and the wound is covered with skin tissue within 24 hours after injury, protecting tissue reconstruction.
Animals living on land are different, and their wounds are often exposed to the air or even in contact with the ground, which means that after the influx of scar tissue, healing work will be difficult to carry out. So the researchers thought of artificially creating a liquid environment for the severed limb area.
They called the new tool BioDome, Dome, which means dome in English, and the dome-like silicone cap that snaps right to the amputated wound of the Xenopus laevis. Inside the hat is a silk protein gel mixed with 5 small molecule drugs (BDNF, GH, 1,4-DPCA, RD5 and RA) that have been shown in previous studies to have a great effect on tissue regeneration, inhibiting inflammation, inhibiting the collagen that causes scarring, and promoting the regeneration of nerve fibers, blood vessels, and muscles.
BioDome is required on the first day of amputation, after which the tissue can grow on its own (Image: Reference[2])
With a constantly stimulating microenvironment, the clawed toad wound receives a signal of regeneration instead of forming some cartilage tip. BioDome devices need to be worn for 24 hours after amputation before they can be removed. There were two groups in the control group, one group did not wear a silicone cover, and the other group did not add 5 small molecule drugs.
From a long-term perspective, the growth rate of the severed limb tissue of the clawed toad using the complete BioDome is significantly faster, of course, this growth cycle is calculated in months, and the experimental group can already clearly see the complete appearance of the clawed toad limbs at the 9th month, while the two control groups basically only form the tip of cartilage.
Over a longer period of time, the limbs of the clawed toad gradually develop more completely, and by about 18 months, the appearance of the limbs has become very similar to that of normal clawed toads. The regenerated new limb not only has the skeletal structure of the natural limb, but also the tissues, including the nerves, are also very complete, and the only regret is that the end toes have not grown bones.
▲Only the use of BioDome in its entirety can regenerate the amputation (Image source: Reference[2])
This newly regenerated limb is fully functional, can move autonomously and respond to external stimuli, and when the researchers touch it with fibers, the clawed toad contracts the new limb. What's even more amazing is that they can use their new limbs to swim in the water, in the same movements as ordinary clawed toads.
This method brought by BioDome not only allows us to see a regeneration miracle, but more importantly, it only needs one treatment to allow the limb to grow on its own within a few months, "The clawed toad actually has the ability to trigger limb regeneration, and it only needs to go through BioDome treatment for several months to start regeneration." Dr. Nirosha Murugan, lead author of the study.
Humans may have this ability, but we need to find the right combination of activators. The next step for the research team will be to test in mammals, looking for regeneration secrets that are closer to humans.
Resources:
[1] Researchers regrow frog's lost leg. Retrieved Jan 27th, 2022 from https://medicalxpress.com/news/2022-01-regrow-frog-lost-leg.html
[2] Nirosha J. Murugan et al, Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis, Science Advances (2022). DOI: 10.1126/sciadv.abj2164.
More recommendations
Click "Watching" and go again