Body regeneration and nerve repair, where are we on the cutting edge of modern medicine?

This article explores the possibilities of body regeneration and nerve repair through modern medical technologies such as stem cells, extracellular matrix, and scaffolds. It highlights recent research and success stories, and explains the impact these technologies will have on the future of medicine.

 

A few months ago, a drama crew member fell from a height and became a paraplegic, and shortly after that incident, a Chinese man’s calf was amputated after his leg got stuck in an elevator. Unlike suffering from a disease, no one can deny the feeling of despair that comes with losing the use of a body part or having a body part amputated. Modern medicine is working to solve diseases caused by viruses and antigens, but at the same time, medical technology is advancing for people who have suffered such accidents. Losing the use of a part of the body usually involves the nerves. This is because the nerves are usually severed or damaged, leaving the body unable to move voluntarily. And amputation of the body seems like a problem that could be solved if cell regeneration were possible. Let’s take a look at the state of modern science and technology in both nerve repair and cell regeneration. Technologies for regenerating and repairing the body can be divided into two main parts: cell regeneration and nerve regeneration.
First, cellular regeneration is divided into two parts: culturing or injecting cells, and expressing the body’s ability to regenerate. The method of injecting stem cells into a specific area has lower regenerative power than cell culture, and there is also a risk of mutating into cancer cells, so research is still underway. In Korea, stem cell procedures are not viewed favorably due to safety and ethical issues, so it will be a long time before they are commercialized for treatment. The cell culture technology that is gaining more attention than the stem cell injection method is a scaffold. Used in conjunction with 3D printing technology, it is primarily used to replace damaged organs. Cell culture alone is not enough to shape an organ, so a scaffold is used. A bio-artificial scaffold made from a biodegradable material called PLGA that naturally breaks down in the body, it can be thought of as a kind of mold that helps stem cells grow into a specific shape. Stem cells are placed into the scaffold and then encouraged to produce body cells that match the damaged organ or skeleton in the body. The advantage of this technology is that patients don’t have to take lifelong immunosuppressants to suppress immune rejection like they would with a traditional organ transplant. Because the scaffold is cultured with the patient’s own cells and blood, it’s safe to say that it’s the patient’s own organ. The main advantage is that it reduces the time and effort required to find the least immunologically reactive organs for transplant patients. So far, 3D printing has been successful in creating kidneys and bladders. If this technology advances, it will make it easier to provide organs to organ-damaged patients in need of transplants without the need for donors.
The extracellular matrix plays a key role in unleashing the body’s regenerative capabilities. The extracellular matrix is the skeleton of the cell, consisting of molecules synthesized, secreted, and accumulated by the cell that binds the cells together. It is the foundation on which cells are built to regenerate. For natural regeneration through extracellular matrix, it is necessary to use a material with excellent regenerative ability. Currently, pig bladder tissue is used in this technique. Pig bladder tissue is characterized by its short regeneration cycle. When the cells were removed from the pig’s bladder and the extracellular matrix was made into a gel and powder and applied to a patient with an amputated finger, the finger cells began to regenerate according to the regeneration cycle of the bladder tissue. Of course, since the extracellular matrix comes from pigs, there’s no way to get rid of the smell of pigs on the fingers, but the fact that the amputated body part regenerated is amazing. This method has even been used to successfully repair severely damaged athletes’ thighs and damaged colon tissue using dog colon extracellular matrix. In the human fetus, the extracellular matrix interacts with the fetal stem cells to help all parts of the body grow. When a fetus is in the womb, it can repair almost any tissue that is damaged. Modern scientists used to believe that the function of the extracellular matrix ceases after the fetus has completed all tissue development, making regeneration via the extracellular matrix impossible. However, the above-mentioned cases of finger and thigh repair using pig-derived extracellular matrix have shown that it is possible to reactivate the regenerative capacity of the fetus. Scientists are working with the belief that extracellular matrix in humans can be activated at the desired time.
In the case of nerve regeneration, the potential for recovery depends on whether the damage is in the central, peripheral, or autonomic nervous system. In general, the axons that make up the peripheral nervous system automatically repair themselves after physical damage. However, if the axons in the central nervous system are physically damaged, they are less likely to recover and are more likely to lose function. In this case, the synapses between nerve cells fail, resulting in a lack of sensation or paralysis of a part of the body. Scientists are working to understand and apply this difference. An example is the characterization of DRG neurons, which make up the sensory nervous system. DRG neurons extend two axons: a central branch to the spinal cord, which is the central nervous system, and a peripheral branch to the sensory organs, which is the peripheral nervous system. When axons located in the peripheral nervous system are damaged, they regenerate quickly and perform their original functions, whereas when axons located in the central nervous system are damaged, their ability to regenerate is significantly reduced and often fails. Interestingly, when the axons in the peripheral nervous system suffer physical damage first, and then the axons in the central nervous system, the central nervous system’s ability to recover is greatly enhanced to match the recovery of the peripheral nervous system. Through this mechanism, scientists believe that if we understand the signaling mechanisms that trigger the regenerative capacity of axons in the peripheral nervous system when they are damaged, we can artificially regenerate and repair damaged nerve cells in the central nervous system. This would be good news for patients who have suffered central nervous system damage and are unable to move parts of their bodies due to neurological problems. There is hope that they may be able to use their paralyzed bodies again.
What limits the regeneration of the central nervous system is the scarring of nerve cells. When the central nervous system, the spinal cord, is injured, scars are created by damage to non-neuronal cells before the nerve cells can activate their regenerative mechanisms. The scar acts as a physical barrier for the damaged axon to reconnect to its original target. Therefore, it is currently a hot topic in embryology to study the signaling mechanisms that activate the regenerative capacity in the first place, as well as how to inhibit scar formation. In addition to scarring, several proteins, such as Nogo, MAG, and OMGP, have been shown to interfere with the regenerative capacity of neuronal axons. Unlike scarring, which acts as a physical barrier, these proteins chemically and directly interfere with axon regeneration. The use of monoclonal antibodies that neutralize these proteins has been shown to alleviate the inhibition of regeneration, suggesting that a more intrinsic approach is needed to maximize the regenerative capacity of neurons.
Biotechnology research is currently accelerating the development of medicine, including methods to regenerate amputation sites through extracellular matrix, artificial organs that are free from immunosuppressive drugs using scaffolds, and the possibility of restoring neurons that have lost their function. Several scientific technologies have developed independently and interrelate with each other. It’s no exaggeration to say that all of the technologies listed above are the result of a combination of unique technologies. This emphasizes how important it is to further study pure science and combine them. In the near future, if we can get better at what we’re doing, humanity will have an easier time living our lives. It would be a huge step forward for biotechnology and medicine.