Limb Regeneration

The differences between the immune responses of a human and salamander determine the limit of their regenerative capabilities.

Reading Time: 3 minutes

While losing a limb appears to be far-fetched, it is the harsh reality of around 185,000 people who have lost their limbs due to reasons ranging from diabetes to trauma in America alone. It may make one envious of the supernatural creatures in books and movies that can regrow their body parts in the blink of an eye. However, once an otherworldly notion, human limb regeneration is becoming more of a reality with recent laboratory triumphs. Last month, scientists from Tuft University and Harvard University successfully triggered the regeneration of the left leg of an adult African clawed frog, a specimen that does not naturally regrow lost limbs on its own. This feat is a significant step toward achieving limb regeneration in humans and potentially improving the lives of millions of amputees.

To regrow the lost limb of the African clawed frog, researchers enclosed the wound of the amputated left leg in a BioDome, a silk protein gel containing a five-drug cocktail. Each drug served a different purpose inspired by the regenerative conditions of a salamander: reducing inflammation, inhibiting collagen production, and encouraging the growth of new nerve fibers, blood vessels, and muscles. The result was a fully functional regrown leglike structure.

Though humans regrowing whole limbs is a figment of science fiction, we are actually capable of regeneration to some extent. For example, our epidermis, the outermost layer of our skin, effectively regenerates skin cells. In fact, our skin regenerates approximately every month while maintaining the same vital defensive functions of our epidermis. Our gut lining, also known as the epithelial, is considered the most regenerative organ in the body, regenerating every five to seven days in order to sustain the processes of the digestive system such as absorbing nutrients and eliminating waste. Stem cells are yet another form of our body’s natural regenerative processes that generate different types of new cells, such as growing nerves and blood vessels. However, as these examples may suggest, our body is only capable of regenerating bits and pieces.

On the other hand, salamanders and other creatures harness the biological potential to regrow tissues, organs, and even entire limbs. Less complex organisms, such as unicellular organisms and invertebrates, are most known to be able to regenerate completely new limbs. Starfish and flatworms can regrow whole bodies from amputated parts. While less complex organisms also have this ability, salamanders are usually used as models for regeneration in labs because of their impressive regenerative abilities as well as a closer evolutionary relationship to humans compared to other organisms, as both humans and salamanders have vertebrae and similar genes for growth and repair.

The difference between a salamander and a human’s regenerative abilities starts with their different immune reactions to injuries. In humans, the immune system is quick to respond, initiating blood clots with the release of platelets and fibrin, which serves as a binding agent for the wound. Then, injured blood vessels near the wound cause localized swelling and signal inflammation, increasing the number of white blood cells. Finally, the wound is healed with the construction of new scar tissue from the protein collagen. It is important to note that this scar tissue does not perform the same functions as the undamaged skin.

Rather than scarring, salamanders send stem cells to the injured area after the blood clots. A blastema, which contains stem cells that are assigned the cell types of the nearby cells of the wound, forms beneath the surface of the wound. Over time, the blastema differentiates and eventually regrows into a functional limb. This process is similar to how we started off in the womb as a blastema. Similar to a salamander’s missing limb, the blastema differentiates into an embryo and the stem cells become assigned to different cell types, eventually creating organs and nervous systems.

By comparing these two bodily functions, the scientists at Tufts and Harvard managed to incorporate the marked characteristics of a salamander’s immune system to the BioDome fluid. As the years go by, technology continues to progress rapidly, and scientists are further revolutionizing mechanisms that are significant to major rehabilitation purposes. With the help of animal models and the refinement of scientific knowledge, we have been able to make discoveries that break the boundaries between science fiction and reality.