In this blog post, we will look at the causes of immune rejection in organ transplants and the potential for xenotransplantation and artificial organ technology to solve this problem.
When cells, tissues, or organs in the body are damaged and can no longer function, they are replaced through transplantation. The cells, tissues, and organs that are transplanted are called grafts. If grafts from the patient or identical twins are not available, grafts from other people are used in “allogeneic transplantation.” However, our bodies cause an immune response when foreign substances enter the body, so they always reject grafts that are not genetically identical.
Immune rejection is caused by differences in the major histocompatibility complex (MHC) molecules expressed on the surface of immune cells. MHC varies from person to person, and the greater the genetic distance between individuals, the greater the difference in MHC, and the stronger the rejection reaction. To prevent this, immunosuppressants are used, which suppress the immune response but increase the risk of disease infection. Transplantation is not only expensive, but also the number of available organ grafts is very limited, so alternative methods are being developed.
One method is to use “electronic artificial organs” such as artificial hearts. However, these are used to temporarily replace organ functions and have disadvantages such as the need for additional power supply and regular replacement of parts. They have not yet reached a stage of sophistication sufficient to completely replace human organs. However, this technology is constantly evolving, and scientists are conducting various studies to improve the performance of electronic artificial organs. These efforts include using biocompatible materials to minimize adverse reactions with organs and developing longer-lasting battery technology.
Next is “xenotransplantation,” which involves transplanting grafts from other animals that are similar to human tissues and organs into humans. However, xenotransplantation causes a much more severe rejection response than homotransplantation. In particular, human natural antibodies react to antigens expressed in cells of other species, causing hyperacute rejection and acute vascular rejection of xenografts.
Experiments have been successful in transplanting grafts obtained from genetically modified mini pigs that have had the genes that cause such rejection reactions removed. Mini pigs have the advantage of having organs similar in size to those of humans and high reproductive capacity, allowing many individuals to be produced in a short period of time, and research is underway to develop xenografts using mini pigs. Another problem with xenotransplantation is endogenous retroviruses. Endogenous retroviruses are parts of the DNA of living organisms that are believed to have originated from retroviruses. They are not active viruses and are present in all mammals, including humans.
Retroviruses are viruses that contain their genetic information in RNA and have reverse transcriptase, infecting specific types of cells. Unlike other organisms, where only the transcription process of RNA from DNA containing genetic information can occur, retroviruses enter the cells of other organisms and convert their RNA into DNA through reverse transcription, inserting themselves into the DNA of those cells and infecting them. After that, like other viruses, they use the host organism’s system to replicate and multiply, and when certain conditions are met, they destroy the host cells.
However, there have been cases where reproductive cells such as sperm and eggs have survived infection by retroviruses. All cells derived from such cells are endogenous retroviruses. Endogenous retroviruses undergo mutations over generations, causing changes in their base sequences, and do not act as viruses within the cells. However, if endogenous retroviruses are removed and injected into cells of other species, they can be converted into retroviruses and infect those cells.
Therefore, technology is being developed to effectively remove endogenous retroviruses from the DNA of mini pigs. If this technology is successfully developed, the safety of xenotransplantation will be greatly improved, providing more patients with the opportunity to save their lives.
Based on the results of previous research on alternative technologies, much research is being conducted to develop ideal transplants. This research is being conducted in collaboration with experts in various fields, such as biotechnology, medicine, and genetics, and it is expected that safer and more efficient transplant technologies will be developed in the future, giving hope to many patients.
