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Axoltol Limb regeneration in humans: How can Science jump from Dreaming fantasy to reality?
15 August 2020
Appendage regeneration occurs by a sequence of events resembling those that take place during development in the embryo. This requires embryonic conditions such as hydration and hyaluronate content where Wnt and other signaling pathways, together with non- coding RNAs, can be re-expressed. These conditions among vertebrates are fully met only in amputated limbs of amphibians, likely because they are neotenic and maintain larval characteristics, including immaturity of their immune system and permanence of numerous stem cells. Although some key genes orchestrating limb regeneration are also present in amniotes, including humans, these genes are not expressed after injury. In amniotes a key problem for regeneration derives from the efficient immune system, largely deficient in anamniotes. As a consequence, wounds and appendage loss tend to scar instead of regenerating. Efforts of regenerative medicine in the attempt to induce the regrowth of limbs in humans must produce outgrowths with high hydration and hyaluronate content in order to create the immune-suppressed conditions similar to those present during development. The induced blastema must be manipulated for long periods of time in order to maintain the same regions present during limb development, an apical epidermal ridge and a polarizing region that forms gradients of expression of Wnt, Shh, FGF, BMP and Hox-genes. Pharmacological treatments to direct the regenerating limb into normal growth without risk of inducing abnormal or tumorigenic growth must be monitored during the course of the regeneration process — a medical treatment lasting years to fully regain the size of the lost appendage.
To begin thinking about how to accomplish human limb regeneration, scientists have taken note of animals that already show this ability. A prime example is the axolotl (Ambystoma mexicanum), a species of aquatic salamander. Unlike humans, it has the “superpower” of regenerating its limbs, spinal cord, heart, and other organs. Humans have also been known to regenerate the tips of the fingers, including the bone and skin. Multiple clinical reports in the past decades have documented such instances following traumatic injury. Unfortunately, this response gets weaker as the site of loss occurs closer to the palm. While this ability has undoubtedly helped some people in the event a traumatic injury, it is a far cry from the axolotl’s ability to regenerate a fully-formed limb with all of its normal muscles, cartilage, and other tissues.
The immune system was found to be an important player the limb regeneration process. Macrophages, which are cells that serve a critical role in the inflammation response after injury, were previously connected to regeneration. Tweaking the nervous system has also been shown to interfere with regeneration. Scientists have observed that surgically removing a limb’s nerves prior to amputation can hinder regeneration, though work is still being completed to better understand why this happens.
All of these previous methods, though, rely on needing to remove an otherwise crucial part of a healthy body (e.g. immune cells and parts of the nervous system). But scientists are now diving down to the level of genes to search for new insights. To accomplish this, researchers first attempted to answer the question of how many times an axolotl limb can successfully regenerate. By comparing the genes that were turned on or off when the axolotl’s limb wasn’t able to regrow, scientists have found more molecules and processes to study that hold promise for kick-starting regeneration in humans. Perhaps one day, drugs can be made to modulate these genes, causing them to turn on and help a human limb to regrow after amputation.
1.“With some help from salamanders, will humans one day be able to regrow limbs?” – STAT
2.“If other animals can regenerate their limbs, why can’t humans?” – Public Radio International
As we advance along with science and technology, we can see that the advancements is growing towards a point where it seemed impossible by the natural process inbuilt. AI, Artificial implants, Regeneration of limbs, Nanobots in therapy, " Superhumans/ Transhumans" by gene mutations and technology, and even prolonging life years or prevention of death are few of the examples.
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