In this blog post, we look at how modern biotechnology, including extracellular matrix, stem cells, and nerve regeneration technology, is expanding the limits of human regeneration.
A few months ago, a drama crew member fell from a high place and was left paralyzed from the waist down. Shortly after that incident, a Chinese man’s calf was severed when his leg got caught in an elevator. Unlike suffering from an illness, no one can deny the despair felt when one loses the use of a part of one’s body or when a part of one’s body is severed. Modern medicine is working to cure diseases caused by viruses and antigens, but at the same time, medical technology for people who have suffered such accidents is also advancing. The inability to use part of the body is mainly related to the nerves. This is because the nerves are usually severed or damaged, making it impossible to move the body voluntarily. And the severing of the body seems to be a problem that can be solved if cell regeneration is possible. We will introduce the current state of modern science and technology in terms of nerve recovery and cell regeneration. Technology related to body regeneration and recovery can be broadly divided into two categories: cell regeneration technology and nerve regeneration technology.
First, cell regeneration can be divided into technologies for culturing or injecting cells and technologies for expressing the regenerative abilities of the human body. The method of injecting stem cells into specific areas has lower regenerative ability than cell culture technology and carries the risk of mutation into cancer cells, so research is still ongoing from various angles. In South Korea, stem cell treatment is not viewed favorably due to safety and ethical concerns, so it is expected to take a long time before it is commercialized for therapeutic use. Cell culture technology, which is attracting more attention than stem cell injection, relies on a scaffold. Used in conjunction with 3D printing technology, this technology is mainly used to replace damaged organs. Since it is difficult to form organs using cell culture alone, a scaffold is used. A scaffold is a bioartificial support made of a biodegradable material called PLGA, which decomposes naturally 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 in the scaffold to generate somatic cells that match the damaged organs or skeleton of the human body. The advantage of this technology is that patients do not need to take immunosuppressants for the rest of their lives to suppress immune rejection, as is the case with conventional organ transplants. Since the cells are cultured on the scaffold using the patient’s own cells and blood, there is no problem with transplanting the organs to the patient. The biggest advantage is that it reduces the time and effort required to find organs with the least immune rejection in transplant patients. To date, kidneys and bladders have been successfully created using 3D printing technology. With further development of this technology, it will be possible to easily provide organs to patients with damaged organs who need transplants without the need for donors.
Extracellular matrix plays a key role in technologies that express the regenerative ability of the human body. Extracellular matrix is composed of molecules synthesized, secreted, and accumulated by cells, and it is the framework that binds cells together. It can be said that extracellular matrix is the foundation for the regeneration of cells. For natural regeneration through extracellular matrix, materials with excellent regenerative ability must be used. Currently, pig bladder tissue is used for this technology. Pig bladder tissue has a short regeneration cycle. Cells were removed from pig bladders, and the extracellular matrix was made into a gel and powder form, which was then applied to patients with severed fingers. The finger cells began to regenerate in accordance with the regeneration cycle of the bladder tissue. Of course, since the extracellular matrix is from pigs, there is no way to eliminate the pig smell from the fingers, but it is amazing that the amputated body parts were regenerated. Using this method, it has been reported that the thigh muscle of a seriously injured athlete and damaged colon tissue were successfully restored using the extracellular matrix of a dog’s colon. In the human fetal stage, the extracellular matrix interacts with the fetal stem cells to help all parts of the human body grow. This can be seen in the fact that almost all damaged tissues can be repaired while the fetus is in the womb. Modern scientists have believed that the function of the extracellular matrix ceases after the fetus has completed all tissue development, making regeneration through the extracellular matrix impossible. However, the case of restoring fingers and thighs using extracellular matrix extracted from pigs mentioned above has shown the possibility of reactivating the regenerative ability of the fetal stage. Scientists are conducting research with the belief that it will be possible to activate human extracellular matrix at the desired time.
In the case of nerve regeneration, the possibility of recovery varies depending on whether the damage is to the central nervous system, peripheral nervous system, or autonomic nervous system. Generally, axons, which make up the peripheral nervous system, recover automatically even if they suffer physical damage. However, when the axons that make up the central nervous system are physically damaged, recovery is difficult and there is a high possibility of losing function. In such cases, synapses between nerve cells cannot be formed, resulting in a loss of sensation or paralysis of part of the body. Scientists are conducting research to understand and apply this difference. An example of this is the characteristics of DRG nerve cells that make up the sensory nervous system. DRG nerve cells, which extend two axons, extend a central branch to the spinal cord, which is the central nervous system, and a peripheral branch to the sensory organs, which are the peripheral nervous system. When the axons located in the peripheral nervous system are damaged, they regenerate quickly and perform their original functions, but when the axons located in the central nervous system are damaged, their regenerative ability is significantly reduced, often leading to failure to regenerate. Interestingly, when the axons in the peripheral nervous system are physically damaged first, followed by damage to the axons in the central nervous system, the recovery of the central nervous system is greatly enhanced in line with the recovery of the peripheral nervous system. Through this mechanism, scientists believe that if they can understand the signal transduction mechanism that triggers the regenerative ability of axons in the peripheral nervous system when they are damaged, it will be possible to artificially regenerate and restore damaged nerve cells in the central nervous system. This is good news for patients who are unable to move parts of their bodies due to neurological problems caused by damage to the central nervous system. It gives them hope that they will be able to use their paralyzed bodies again.
The factor that limits the regeneration of the central nervous system is scarring of nerve cells. When the spinal cord, which is part of the central nervous system, is damaged, scarring occurs due to damage to non-nerve cells before the regeneration mechanism of nerve cells is activated. This scarring acts as a physical barrier in the process of damaged axons reconnecting to their original targets. Therefore, the current topic of embryology is to study the signal transduction mechanism that activates the aforementioned regeneration ability and, at the same time, to study methods to suppress scar formation. In addition to scars, it has been found that several proteins, such as Nogo, MAG, and OMGP, interfere with the regeneration ability of nerve axons. Unlike scars, which act as physical barriers, these proteins directly interfere with the regeneration of axons through chemical means. The use of monoclonal antibodies that neutralize these proteins has been shown to alleviate the inhibition of regeneration, and there is a growing opinion that an intrinsic approach is necessary to maximize the regenerative capacity of nerve cells.
Biotechnology research is currently accelerating the advancement of medicine, including methods for regenerating severed limbs using extracellular matrices, artificial organs that do not require immunosuppressants using scaffolds, and the possibility of restoring lost nerve cells. Various technologies have developed independently and are now interconnected. It is no exaggeration to say that all of the technologies introduced above are the result of combining unique technologies. This reminds us once again of the importance of further research in pure science and the fusion of different fields. If the above research yields better results in the near future, humanity will be able to live more comfortable lives. I believe that this will lead to tremendous advances in biotechnology and medicine.
