What are the problems/ knowledge gaps in realizing the dream of endogenous limb regeneration?

What are the problems/ knowledge gaps in realizing the dream of endogenous limb regeneration?


Limb regeneration is all about regrowing lost limbs in humans suffering from life-changing injuries. But are the limbs regrowing process possible in humans? Do you think it could be possible in the future? Still, the research is going on to realize the dream of endogenous limbregeneration. You must know that this limb’s regeneration process is associated with profound morbidity, life-long disability, and mortality. The new technique of limb salvaging is considered as the novel treatment in regenerative medicine. It allows the physician with a better and effective option in repairing and saving a damaged limb. The novel and effective therapies of limb loss are required urgently.

The two main and emerging approaches in regenerative medicine are tissue engineering and harnessing endogenous regenerative potential. In the tissue engineering approach, stem cells and biomaterials are used to rebuild a lost limb. But it includes some major drawbacks like this stem cell therapy is of high cost, tumorigenic potential, and immunological considerations. This effective approach comes with success only when only one tissue needs to be regenerated. The harnessing endogenous regenerative potential has come up as a promising approach that potentially overcomes the obstacles related to cell transplantation. It is essential that in limbs, multiple component tissues must be reorganized like skin, bone, tendons, nerves, muscle, cartilage, blood vessels, and adipose tissue for the success of the regenerative process.

When you look at a lizard, you might be stuck with the thought of how they grow a tail after it’s been cut. Well, let us say that they do with the scientific process called regeneration.

As the name suggests, it is a process where the cells of an organism develop to create a replica of a part they lost or shed. In simple words, once an orgasm sheds or loses a part of themselves, they produce some cells and tissues similar to their lost part and replace it with the new one.

Of course, it is possible for every organism, including humans to restore or regenerate. regeneration can either be complete, where the tissues are formed and are performing the functions as required, or are incomplete but still complete enough to serve their purpose.

Why do humans lose Regeneration ability with age?

Salamander could easily grow back their leg if you cut the leg off. But in the case of humans, this is not possible, and there are many reasons. Due to changes in the satellite cells and the muscle stem cells, there is a huge decline in regenerative muscle potential. With age, the satellite cell numbers decline gradually in mammalian muscles. Hence you must have noticed that the adult mammals have a very limited regenerative capacity. As per the data, the process of limb regrowing is conserved across species. But is there any possibility that if we want, there is a possibility that we could also reactivate our latent embryonic regenerative capacity?

The most focused and interesting study is the regeneration ability of reptiles, birds, and mammals. As per most of the evidence, it is confirmed that regeneration is a primordial feature of animals. This process involves a longer period of regrowth, and tissue redifferentiation is delicate. Due to aging, there might also be inadequate elasticity, which may lead to inappropriate regeneration, potentially leading to cancer. One of the most prominent pathogens and carcinogens is aging. In human’s skin, intestines, and red blood cells are constantly renewing throughout adult life. And every five days, the lining of the human small intestine is essentially made afresh. An injury that is induced to fingertip regeneration in human children and young mammals has been documented. But the regeneration processes related to limbs in humans are still not possible. But various studies are done to make it possible.

In a study, it has been observed that a regenerative decline in mammals with immune system maturity. But in humans and mice, the regenerative capacities are limited. And the limitation is up to fetal and juvenile digit tip regeneration. In several models, anti-inflammatory is permissive to regenerative processes and in line with an anti-inflammatory drug, results to facilitate regeneration. The loss of functional fitness of some of the organisms is the main reason for the loss of regeneration that is suggested through some studies. There are different model organisms and systems that have highlighted the factors that constrain the regenerative process as per various studies.

 There is a certain regenerative capacity in the human tissues, and this capacity could be increased by modulating the niche with factors like growth, hyaluronic acid content, and electrical stimulation. For Limb regeneration, it is essential to identify the problems. And after identifying the problems, it is essential to solving them. There are many mysteries in the process of limb regrowth of the mammals that must be solved for the experiments’ success. The current knowledge gap must be filled in an effective way to increase the chances of getting the dream of endogenous limb regrowth.

Regeneration in animals

Arthropods- these organisms perform regeneration when they lose a part of their body or for the autotomy. The hemimetabolous insects can regenerate only in their final stage of molting.

fortunately, this isn’t the case with crustaceans. they are the ones who are capable of regenerating throughout their existence.

Arachnids are insects that can regenerate the venom they produce. A famous species of this type are the Scorpios.

Annelids- Annelids are the segmented worms you see almost anywhere where the wet and moist climate is present. Although, these are the ones known for their regeneration powers. you could chop them into a hundred tiny pieces and you can see them growing.

Want a piece of advice? never chop a worm in your yard because you will just find more of it.

the lumbriculids are quite capable of regenerating from segments while other types like the leeches and Branchiobdellis aren’t that powerful.

Echinoderms- when we talk about echinoderms, the first thing that comes to mind is jellyfish! one of the oldest living organisms on the planet. They are pretty popular for the regeneration power over the tissues that they possess.

They take about 4 weeks to regenerate an appendage.

now, there are some other organisms that can regenerate internal organs, including portions of their nervous system.

Planaria- Planarias use a phenomenon called the degrowth where they use the energy from its cells to avoid any sort of starvation.

they perform an excellent show in growing out their lost parts in much lesser time.

you can cut them in two halves anywhere and get two new individuals. they barely take a week or two to develop into a whole new being, doesn’t matter what its starting stage was.

Amphibians- when it comes to Tetrapods, they are the most impressive ones with the regeneration techniques. An example of this is the salamanders you have heard of. they are extraordinary at reshaping their limbs after an accident or it is separated from their body.

the salamanders regenerate their limbs in two steps, first where they try to form a blastema around their wound.

second, they will have to undergo some proliferation of cells, patterning of them, then, differentiating in them, and lastly, tissue growth to complete the process.

Hydra- the unicellular organisms that can regenerate from scratch to a fully formed and developed body.

the main support that helps the regeneration can be achieved from the length that the stem cells possess.

when they are separated, they are most likely to form two new hydras of the same size.

Aves- while some of the organisms possess impeccable regeneration abilities, Aves, as in, the birds lack some possession.

they aren’t gifted with much regeneration power. Although, some studies have discovered that the limbs of a bird can be regenerated but according to the place of injury or loss that they might have suffered through.

Humans- you know that you can grow new skin cells at any given point and so can you grow nails after cutting them.

Well, humans can also regenerate a few organs in their bodies like the bladder, the penis, and the vagina.

other than that, we can also regenerate tissues and cells such as the red blood cells and the rebuilding of the uterus when a female human performs the process of menstruation.