By Laura Tran, C2ST Intern, Rush University

When we get hurt, our bodies are capable of closing cuts and mending broken bones. We can even use stem cells to regrow parts of our liver¹. But this is basically the extent of our regeneration capabilities. Although our bodies naturally form scar tissue at major injury sites to protect them from blood loss and infection, we generally can’t recover tissue loss or reverse it (in the case of limb loss, as an example). It may be the case that we cannot regrow lost arms or legs due to the complexity of these limbs. 

Although we cannot naturally regrow limbs, there are a few animals that are capable of full regeneration³ such as salamanders, starfish, crabs, and lizards. Recent research in animal models has brought us a step closer to achieving regenerative medicine.

In their tadpole or froglet (young frog) stage, African clawed frogs (Xenopus laevis) are able to regenerate limbs. However, as adults, these frogs slowly lose their regenerative abilities. Scientists⁴ at Tufts University have been able to trigger the regrowth of legs in adult African clawed frogs.

In this recent study, scientists surgically amputated frogs’ legs and placed a wearable silicone cap, called a “BioDome” over the wounded area. Because many of the animals capable of regeneration reside in aquatic environments, the BioDome was designed to mimic a liquid (or amniotic) environment to jumpstart the healing process. 

Additionally, the BioDome contains a “drug cocktail” to help regenerate lost limb tissue. The five drugs in the cocktail each serve a different purpose, such as preventing collagen production (which causes scarring) and reducing inflammation. Growth hormones were also included to encourage the growth of new nerves, muscles, and blood vessels. In a previous study⁵, the BioDome utilized a single drug, progesterone, to stimulate limb regrowth. The limb grew a long flap of tissue called a “spike” and developed a greater sensitivity to touch, but it was still a far cry from being a functional leg.

During the study, the BioDome was used in the first 24 hours post-amputation to kick-start the regenerative healing process, circumventing the body’s natural tendency to close up the wound with scar tissue. After a few days of treatment, the frogs activated molecular pathways (e.g., Wnt/β-catenin, TGF-β, hedgehog, and Notch) that embryos show during development. This demonstrates that researchers can trigger inherent regeneration pathways in adult frogs under the right conditions.

The frogs were observed over an 18-month regrowth period. Over time, bones, blood vessels, and functional nerves formed within the regrown limb–the makings of a functional leg! The frogs were able to walk and swim nearly as well with their regenerated leg as they did before their leg amputation.

Millions of people have lost their limbs to disease² (i.e., diabetes or peripheral artery disease) or trauma (i.e., accidental injury or military combat). Current prosthetics and bionic technology are advanced but are still limited in terms of mobility. Therefore, regenerative medicine has the potential to greatly improve patients’ quality of life. The BioDome is a testament to how much of a game-changer this work is in the field of regenerative medicine! The use of a drug combination in a wearable bio-device can jumpstart the regenerative process and form a functional limb. The next step (no pun intended), for researchers, is to implement this technology in mammals.

References:

1. https://pubmed.ncbi.nlm.nih.gov/19470389/
2. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/amputation#:~:text=Amputation%2C%20Diabetes%20and%20Vascular%20Disease,in%20toes%2C%20feet%20and%20legs.
3. https://www.nigms.nih.gov/education/Documents/fact-sheet-regeneration.pdf
4. https://www.science.org/doi/10.1126/sciadv.abj2164
5. https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31573-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718315730%3Fshowall%3Dtrue