In this blog post, we’ll explore how tissue engineering is used to cultivate artificial tissues, as well as how cell removal and repopulation techniques are applied.
Tissue Engineering and Artificial Tissue Cultivation
Have you ever seen the movie ‘Face/Off’? Starring Nicolas Cage, this action film thrillingly explores the intriguing question, “What would happen if my face were replaced with someone else’s?” through a high-stakes showdown between the FBI and a criminal organization. When the movie was released in 1997, such technology felt like a fantasy far removed from reality, but today, tissue engineering is being utilized as an actual medical technology through research and clinical applications in various fields.
So, what exactly does tissue engineering entail? Tissue engineering is a field of study that, based on the principles and technologies of life sciences, medicine, and engineering, develops tissues capable of replacing or regenerating damaged biological tissues or organs, thereby enabling the maintenance, enhancement, and restoration of biological functions. Recently, research has been actively conducted not only on the regeneration of tissues such as skin, cartilage, and blood vessels but also on the development of artificial organs, and it is gaining attention as a new treatment option for patients in need of organ transplants.
Decellularization and the Role of the Extracellular Matrix
In the process of creating such artificial tissues, a tissue engineering technique called decellularization is used. Decellularization is a technique that removes cells present in existing tissue to reduce the immune response that can occur during transplantation. The human body reacts very sensitively to foreign substances. Even a fever caused by infection with pathogens is the result of an immune response aimed at eliminating foreign substances. The same applies to organ transplantation. If a person receives a kidney from another person rather than their own, the immune system may recognize it as a foreign substance and trigger a rejection response. Therefore, to minimize such immune reactions, a process of removing existing cells through decellularization is necessary.
To understand decellularization, we first need to learn about the ECM (Extracellular Matrix). It is generally understood that cells come together to form tissue. However, in reality, a structure called the ECM is essential for cells to form tissue. If we compare cells to people, the ECM is like the buildings in which people live. Just as people need the space of a building to live and carry out their activities, tissue cannot function with cells alone; it requires a structure in which cells can settle and function. The ECM plays precisely that role. Ultimately, decellularization is a technology that removes cells while leaving behind the ECM—this skeletal structure—thereby laying the foundation for the creation of artificial tissue.
Generally, decellularization employs either the freezing-thawing cycle or the detergent method. The freezing-thawing cycle is a method that exploits the differences in physical properties between cells and the ECM to selectively damage the cells. Through repeated cycles of freezing and thawing, the cells are destroyed while the ECM is preserved as much as possible. The chemical treatment method uses surfactants and other agents to remove cell membranes while maintaining the ECM structure. Through these processes, pure ECM from which cells have been removed can be obtained.
The Future of Repopulation and Tissue Engineering
The ECM obtained in this way can be repopulated with the patient’s own cells to create new tissue. Stem cells play a key role in this process. Stem cells possess the ability to differentiate into various types of tissue. Even the same stem cell can become a liver cell, a heart cell, a skin cell, or a bone cell, depending on its surrounding environment and signals. Therefore, the core of tissue engineering lies in regulating stem cells so that they differentiate precisely into the desired tissue.
This is also why ECM from another individual is obtained through decellularization.
With current technology, it is difficult to perfectly replicate the human ECM and the complex signaling system operating within it. In contrast, the ECM of the kidney retains various biochemical signals that induce stem cells to differentiate into kidney cells. Therefore, when a patient’s stem cells are cultured on the decellularized kidney ECM, the patient’s cells differentiate into kidney cells within the ECM. In tissue engineering, this process is called “recellularization.”
This technology offers new treatment possibilities for people with damaged body parts, those with severe skin damage, and those in need of organ transplants. In particular, while the number of patients awaiting organ transplants continues to rise, there remains a shortage of donor organs. Given this reality, tissue engineering and regenerative medicine technologies are gaining attention as important research fields capable of addressing the organ shortage problem, and it is expected that continued advancements will provide new treatment opportunities for more patients in the future.
