Stem cell research is opening new possibilities for treating incurable diseases. We explore how it is transforming human health through innovative therapies and the latest research trends.
The 21st century we live in is the era of biotechnology. And it would not be an exaggeration to say that stem cells are one of the greatest driving forces propelling this biotechnology era forward. Much like the Industrial Revolution in past industrial sectors, a complete understanding of stem cells represents a medical treatment revolution surpassing any previous industrial revolution. Stem cell research is actively progressing worldwide, and its outcomes are already impacting our lives.
Stem cells are cells possessing the ability to differentiate into various types of bodily tissues, i.e., ‘undifferentiated’ cells. There are three main types: embryonic stem cells formed during the initial division of a fertilized egg, adult stem cells found within mature tissues, and induced pluripotent stem cells, which can reprogram fully developed cells back to a pre-differentiation state.
The existence of stem cells was first discovered by Tilley and McClough in 1961. They discovered adult stem cells while conducting cancer treatment research experiments using mice. When mice were exposed to radiation, they developed bone marrow deficiency. Transplanting normal bone marrow cells then restored the mice’s bone marrow deficiency. This experiment revealed the presence of hematopoietic stem cells within bone marrow cells, capable of generating new blood cells. Adult stem cells are undifferentiated cells found within the ‘differentiated’ cells of tissues or organs. Because they are undifferentiated, when transplanted into tissue, adult stem cells can reliably differentiate into the appropriate tissue type without the potential to become cancer cells. Additionally, they offer the advantage of avoiding immune rejection since they are the patient’s own cells. However, their limitations include a very restricted ability to differentiate into various tissues, making them difficult to apply to all parts of the human body. Furthermore, since only very small numbers of these cells exist in each tissue, obtaining large quantities is challenging. Additionally, due to the risk of immune rejection, donation and transplantation are difficult.
In 1988, Dr. James Thomson’s team in the United States established the concept of human embryonic stem cells. Embryonic stem cells are cells obtainable from a fertilized egg created by the union of sperm and egg. Just as a single embryonic cell can differentiate into all cell types to form a complete human organism, embryonic stem cells can differentiate into any cell type. This core concept holds that they could potentially treat various human diseases. The process of extracting embryonic stem cells is as follows: The nucleus is removed from a somatic cell of a healthy individual. This somatic cell nucleus is injected into an egg cell from which the nucleus has been removed. Fusion of the two cells yields cells in an embryonic state. These embryonic-state cells are cultured to create a blastocyst embryo. Once the blastocyst is formed, it differentiates into an inner cell mass and outer cells. At this stage, the inner cell mass possesses pluripotency, meaning it can differentiate into all types of somatic cells. Therefore, stem cells are extracted from the inner cell mass of the blastocyst and differentiated into various cell types. Embryonic stem cells have the advantage of being technically easier to obtain than adult stem cells and can be maintained in an undifferentiated state for a long time in a test tube. If embryonic stem cells could be used to infinitely produce organ cells for treating various incurable diseases in vitro and then transplanted, humanity’s dream of living long and disease-free would be realized. This is an essential technology in the current reality of insufficient donated organs. Currently, attempts are being made to treat patients with conditions like leukemia, Parkinson’s disease, and diabetes by externally culturing and injecting healthy cells to replace the damaged cells.
Moreover, above all, it could offer new hope to infertile couples. While various methods have been explored for couples unable to conceive normally due to sperm issues, the somatic cell nuclear transfer mentioned above enables fertilization without sperm, opening a path to solve this problem on an entirely different level. By using the mother’s egg for the cytoplasm and the mother’s or father’s somatic cell for the nucleus, it becomes possible to have a daughter who closely resembles the mother or a son who closely resembles the father. Furthermore, using embryo splitting technology, embryos can be examined before implantation into the uterus to filter out defective ones or correct specific genes, enabling the birth of a desired healthy baby.
However, embryonic stem cells also have significant drawbacks. Controlling their differentiation is extremely difficult, posing a risk of developing into cancer cells and demanding high technological precision. Furthermore, the supply of eggs faces legal and ethical hurdles, and the necessity of destroying embryos—potential lives—to save a patient’s life fuels considerable debate from a bioethical perspective regarding the use of embryonic stem cells. An embryo is a stage prior to becoming a fetus, and depending on one’s perspective, it may be difficult to consider it a life. However, given that embryonic stem cells will inevitably develop into a human being, various arguments exist across different religions and beliefs that the bioethics applicable to humans must also be applied to embryos. Consequently, research in this area has not progressed actively. Furthermore, most countries have enacted bioethics laws. In Korea, the ‘Act on Bioethics and Safety’ has been established. This law prohibits the use of embryos for the purpose of creating embryonic stem cells. Therefore, conducting embryonic stem cell research in Korea presents practical difficulties, as only sperm, unfertilized eggs, or frozen embryos scheduled for disposal after infertility treatment can be used, making explosive research growth unrealistic.
Due to these bioethical issues, a new type of stem cell has emerged: induced pluripotent stem cells (iPSCs), also known as reprogrammed stem cells. Induced pluripotent stem cells are cells that have been reprogrammed from differentiated somatic cells back to a pre-differentiation cellular stage. By introducing and expressing four specific genes that induce reprogramming into a patient’s skin cells, or by extracting the reprogramming-inducing proteins produced by these four genes and re-injecting them into the skin cells, the skin cells become stem cells capable of differentiating into various tissues, similar to embryonic stem cells. These are called reprogrammed stem cells. In 2006, Professor Shinya Yamanaka’s team succeeded in creating stem cells with the ability to differentiate like embryonic stem cells by introducing genes into mouse skin cells. This achievement was so significant that it earned them the 2012 Nobel Prize in Physiology or Medicine, making induced pluripotent stem cells a truly remarkable discovery. This achievement is so monumental it necessitates rewriting the entire textbook of human biotechnology. It clearly represents a tremendous accomplishment of 21st-century biotechnology, demonstrating that humans can attain regenerative capabilities akin to those of lizards, which can regenerate limbs, spines, and more. It offers tremendous hope for burn victims, those who have lost limbs later in life, and patients with spinal cord injuries. While embryonic stem cells faced ethical issues due to their direct use of women’s eggs and the risk of immune rejection when transplanted into patients, induced pluripotent stem cells hold great significance as they simultaneously resolve these ethical and technical challenges.
Recently, stem cell research has advanced further, bringing revolutionary changes to the treatment of various diseases. Since the 2020s, stem cell therapies have demonstrated their efficacy and safety through numerous clinical trials. Notably, combining them with CRISPR-Cas9 gene editing technology allows for more precise control over stem cell differentiation. This has broadened the range of treatable diseases, enabling the management of complex conditions previously unattainable with conventional therapies.
Recently, in 2022, a U.S. research team successfully regenerated heart tissue damaged by heart attack using stem cells. This research offered significant hope to heart attack patients and opened the possibility of applying stem cell therapy to more cardiovascular diseases. Furthermore, in 2023, a Japanese research team successfully regenerated pancreatic beta cells in diabetic patients using induced pluripotent stem cells. This breakthrough opened the door for diabetes patients to live normal lives without insulin injections.
However, as research is still actively ongoing, unknown side effects could potentially arise. For instance, there are concerns that it could cause mutations or other genetic abnormalities, and there is also a risk of tumor formation during the genetic modification process of reprogramming somatic cells into stem cells. Therefore, extensive follow-up research is necessary to ensure safe use for patients.
To summarize, stem cells are undifferentiated cells with the ability to differentiate into various tissues. Since the discovery of stem cells, extensive research and development have continued. The history of stem cell research has focused on solving problems that arise when applying stem cells to the human body. To overcome the biggest problem with adult stem cells—their limited tissue differentiation capacity—embryonic stem cells were discovered. To overcome the ethical issues surrounding embryonic stem cells, induced pluripotent stem cells were discovered as a new breakthrough. Humanity has pioneered new methods whenever confronted with problems, and we believe today’s challenges will eventually be resolved. Since the 2020s, fusion research with gene editing technology has been actively progressing, leading to the development of more sophisticated and safer stem cell therapies. Therefore, if the currently impossible differentiation control of induced pluripotent stem cells becomes feasible, humanity’s long-cherished dream of liberation from disease may not be so far off.
