How can axolotls grow new limbs?

In the United States alone, almost 2 million individuals suffer from limb loss. While many occurrences of limb loss are associated with traumatic events such as vehicle accidents, the vast majority of cases are associated with disorders that impair the body’s blood vessels. 

 

Diabetic neuropathy is one such illness, in which a patient’s lower extremities gradually lose blood flow over time, finally resulting in the loss of the limb in its entiret. 

 

A rise in the prevalence of diabetes will almost certainly result in an increase in the number of persons who will have to deal with amputation of limbs in the coming years. Unfortunately, the treatment alternatives available now after amputation are little different from those available centuries ago, with prosthetic limbs continuing to be the sole choice for replacement of lost limbs.

 

 

 Nevertheless, although replacement prosthetic limbs have been successful in restoring the appearance of a missing limb, their functionality has remained severely limited, particularly when the lost appendage is a complete arm or leg. 

 

Isn’t it possible that one day, rather of having to depend on an impersonator made of wood or metal, we might simply regenerate a missing limb ourselves?

Animals that can regenerate include several species of birds and mammals.
Scientists have taken notice of animals that have previously shown the potential to regenerate limbs in order to begin thinking about how to achieve human limb regeneration. 

 

 

The axolotl (Ambystoma mexicanum), a species of aquatic salamander from Mexico, is a good illustration of this point. Unlike humans, it possesses the “superpower” of regenerating its limbs, spinal cord, heart, and other organs when they are damaged or destroyed.. 

 

 

Many invertebrates (animals without a spine) are masters of regeneration, and the axolotl is not the only member of the animal world that is capable of doing so.

 

 

 

 Several animals, such as flatworms and hydra, have the ability to regenerate their whole bodies from a single fragment of their previous bodies. Even among vertebrates (animals with spines), the axolotl isn’t the only animal capable of regenerating its own body. 

 

 

Despite the fact that young frogs have the potential to regenerate limbs, as they transition from tadpoles to adult frogs, this ability is lost to them. The axolotl, on the other hand, keeps it throughout its whole life, making it a one-of-a-kind vertebrate and an excellent model for studies into regeneration.

 

 

 

Many creatures go through a process of regeneration, including humans (at least to some degree). While the axolotl is not the only animal capable of regeneration in the animal world, it is the only vertebrate that has the ability to regenerate a large number of body parts during the course of its lifetime.

 

 

The fact is that although there are no known mammals that can entirely regrow lost limbs (humans included), many animals, including humans, seem to be capable of doing so. It has been shown that mice can regrow the tips of their toes, yet loss of toes farther up the foot results in the same scarring that people experience following amputation. 

 

 

Aside from that, humans have been seen to regrow the tips of their fingers, including the bone and skin. Following a catastrophic injury, several clinical studies have been published over the last few decades documenting similar occurrences. Unfortunately, when the place of loss moves closer to the palm, the strength of the reaction diminishes. 

 

 

 

This skill has probably assisted some individuals in the case of a devastating injury; but, it is a long cry from the axolotl’s ability to regenerate a fully-formed limb with all of the regular muscles, cartilage, and other tissues that it had.

 

 

 

I’m not sure how it works, but it does.

When it comes to axolotls, the procedure that ends in the regeneration of a full limb  entails an intricate orchestration of the limb’s remaining cells. In the event of limb loss (B), blood cells form a clot at the location of the incision, which stops the bleeding very immediately and effectively. 

 

 

Following this, a layer of cells attempts to cover the plane of amputation as rapidly as possible, generating a structure known as a wound epidermis in the process (C). 

 

 

Cell division and growth in the wound epidermis are very fast during the first few days after the wound has been closed. A blastema is a cone-shaped structure formed by the fast division of the cells underneath the epidermis that appears shortly after the epidermis (D). 

 

 

Bone, cartilage, muscle, or other cells that de-develop (lose their identity) and become akin to stem cells, which are cells that have the ability to differentiate into any of a variety of cell types, are believed to make up the blastema. 

 

 

In contrast, blastema cells have limitations in terms of the types of cells that they can re-form: for example, a blastema cell that was previously a muscle cell can only re-form different types of muscle cells, not skin or cartilage cells; a blastema cell that was previously a skin cell can only re-form different types of skin cells. 

 

 

 

In the blastema, these de-differentiated cells mature into fully-developed bone or skin cells after growing and multiplying for a number of years (E). Eventually, as the blastema and its cells continue to divide, the expanding tissue flattens and resembles an exact replica of the amputated limb, complete with nerves and blood arteries that are attached to the rest of the body (F).

 

 

 

In order to restore the missing appendage, axolotl limbs go through a multi-stage process, as seen in Figure 2. Despite the fact that skin, bone, cartilage, and muscles may be regrown several times, there is no evidence of harm.

 

 

 

The axolotl teaches us a much.

Researchers must get intimately acquainted with the alterations that axolotl cells experience during regeneration before they can even begin to consider how we may one day be able to regenerate missing human limbs.

 

 

 Among the approaches that have been effective so far is the discovery of molecular adjustments that cause an axolotl to lose its regenerative capacity, which may be used to identify the most critical components and contributors to the process of regeneration. 

 

 

When it comes to limb regeneration, researchers have discovered that the immune system plays a significant role. Previously, macrophages, which are cells that play a vital part in the inflammatory response after an injury, were thought to be involved in the process of regrowth.

 

 The use of a medication to clear out macrophages from an axolotl’s leg prior to amputation, on the other hand, results in the buildup of scar tissue, rather than its regeneration. 

 

 

When a protein called collagen becomes disorganized, it causes scarring. In humans, this is a common part of the healing process, but in axolotls, it is rare. Macrophages seem to be necessary for regeneration, based on this finding. 

 

 

 

It has also been shown that tinkering with the nervous system might impair regeneration. In recent years, scientists have found that surgically removing a limb’s nerves prior to amputation might cause regeneration to be hindered, however more research is needed to determine why this is the case.

 

 

In contrast, all of the approaches described above depend on the necessity to eliminate something that is normally necessary for a healthy body to function well (e.g. immune cells and parts of the nervous system). In order to get fresh insights, scientists have begun to look at the cellular level of DNA. 

 

 

This was accomplished by attempting to answer the issue of how many times an axolotl limb can effectively regenerate before moving on to the next phase. 

 

Researchers discovered that by the sixth time they had amputated limbs, few had recovered to their original size and strength. The researchers also discovered considerable scar tissue build-up when they examined the limbs that were unable to recover further, which was similar to what they had seen in humans after suffering a wound. 

 

 

 

Using gene expression data from the axolotl’s leg that was unable to recover, scientists discovered more substances and processes to investigate that have the potential to aid in the reactivation of human regeneration. 

 

 

Perhaps, in the future, medications will be developed that will control these genes, prompting them to switch on and aid in the regeneration of a human limb after amputation is performed.

 

 

In the future, we should consider

While we are still a long way from being able to regenerate a human limb, we put ourselves at a distinct disadvantage if we do not understand how regeneration happens in the fortunate species that already possess this “superpower,” which is called regenerative capacity. 

 

 

With the use of instruments that enable scientists to study the precise genetic intricacies of the regeneration process, we are slowly but steadily getting closer to knowing what makes the process tick. 

 

 

 

This is being tested by scientists who are working tirelessly to develop new tools that will allow them to identify additional targets and begin transferring these insights to mammals such as mice, meaning that perhaps one day, the millions of people who have lost limbs will have a new treatment option available to them.