Stem cell research has come a long way since the Russian Alexander Maximov coined the concept in 1908. Embryonic stem cells, adult stem cells, and induced pluripotent stem cells each have their own characteristics, advantages, and disadvantages, and their differentiation capabilities and therapeutic potential are constantly being explored. Currently, adult stem cells are widely used for treatment due to their ethical issues and stability, while induced pluripotent stem cells are the cell therapy of the future.
In 2004, Professor Woo-Seok Hwang of South Korea announced that he had successfully cloned embryonic stem cells from human eggs. Although the results of this study were eventually proven to be false, this event increased public interest in the concept of stem cells in Korea. However, interest in stem cells has been around for a long time before that. Starting with the Russian Alexander Maximov’s concept in 1908 and the first proof of their existence by McCullough and James Till in 1963, research on stem cells and their potential to treat diseases has continued in various fields.
Especially in the latter half of the 20th century, stem cell research has advanced rapidly with advances in biotechnology. For example, in 1981, Martin Evans and Gail Martin succeeded in isolating embryonic stem cells from mice, which became the basis for human embryonic stem cell research. Then, in 1998, James Thompson succeeded in culturing human embryonic stem cells for the first time, marking the beginning of human stem cell research. Although steady progress has been made in stem cell research, it has faced various limitations, such as difficulties in controlling stem cell differentiation and ethical issues, which have hindered its progress. However, in 2007, Shinya Yamanaka succeeded in developing iPS stem cells that overcame all of these limitations, reigniting stem cell research, which is still being researched with various therapeutic possibilities.
In this article, we will discuss what stem cells are, their characteristics, the different types, their advantages and disadvantages in research and treatment, and how they can be applied to treatment and research.
Our bodies are made up of hundreds of different cell types, each with a specific function. For example, skin cells isolate the body from the outside environment, lung cells exhale carbon dioxide and take in oxygen, and small intestine cells absorb nutrients into the body. The cells that give rise to these different types of cells are stem cells, which are undifferentiated cells that have the ability to differentiate into these different types of cells. So, in a broad sense, a fertilized egg is a stem cell because it has the ability to divide and differentiate into the entire body. However, when we use the term “stem cell” in general, we are referring to any cell that has the ability to differentiate into a cell other than the fertilized egg.
All stem cells have two properties: the ability to replicate themselves and the ability to differentiate. Unlike other cells, stem cells are able to replicate themselves through somatic cell division in order to maintain their numbers in vivo, so that when they differentiate into two cells, only one of them will differentiate into a cell with a new function, and the other will replicate in the same form as the original stem cell. In vivo, if one stem cell differentiates into two new cells, the other stem cell maintains its number by producing two identical stem cells through somatic cell division. The second property is the potential to differentiate into different cells, or differentiation capacity. Stem cells are divided into totipotent, pluripotent, and multipotent stem cells based on the extent of this differentiation capacity. Totipotent stem cells are stem cells that have the capacity to differentiate to give rise to an intact organism, such as a fertilized egg and the cells that undergo cell division to form the mulberry-shaped blastocyst. Pluripotent stem cells are stem cells found at a slightly more differentiated stage of these totipotent stem cells, and while they cannot give rise to a placenta and thus cannot give rise to a whole organism, they have the capacity to differentiate into almost any cell. These include endodermal, mesodermal, and ectodermal cells, which are further differentiated from the previous loss-of-embryonic state. Finally, pluripotent stem cells are limited in the types of cells that can differentiate from a stem cell, and are mainly limited to cells with similar functions. For example, neural stem cells (NSCs) can only differentiate into cells in the nervous system, such as neurons, astrocytes, and microglia, which are pluripotent stem cells.
Stem cells have the ability to differentiate into other cells as described above, making them highly valuable in therapeutic applications. In order for stem cells to be used in various therapeutic fields, they must have good differentiation capabilities, be able to control the rate of differentiation, have no ethical issues, and not cause immune rejection in patients. Stem cells can be broadly categorized into three types: embryonic stem cells, adult stem cells, and induced pluripotent stem cells (iPS cells), each of which exhibit different characteristics. Let’s take a look at what each of these three types of stem cells are, and the advantages and disadvantages of using them for therapeutic purposes in relation to the characteristics we’ve discussed.
First, embryonic stem cells are the stem cells that are responsible for giving rise to the cells that perform the various functions of a fertilized egg, called a blastocyst, as it undergoes cell division to form tissues, organs, and the fetus. Embryo refers to the period of about 8 weeks after a man’s sperm meets a woman’s egg to become a fertilized egg, and then completes differentiation into various tissues and organs. Embryonic stem cells play a big role in this period, as they are the stem cells that are responsible for giving rise to the cells that make up all the tissues and organs of the fetus, so they have the potential to differentiate into any cell in the body in theory. For this reason, embryonic stem cells are classified as pluripotent and totipotent stem cells as described above. However, embryonic stem cells pose an ethical problem because they are viewed as a living organism, and experimenting with them is tantamount to killing a human being. In addition, embryonic stem cells differentiate very rapidly, making it difficult to artificially control their differentiation rate and direct them to become the specific cells you want them to become, and there is a risk that they could develop into cancerous cells. Furthermore, if you need to transplant someone else’s embryonic stem cells, this is problematic because it can lead to immune rejection. To address the issue of immune rejection, personalized embryonic stem cells have been developed. Personalized embryonic stem cells are created by culturing a fertilized egg by removing the original nucleus of the fertilized egg and injecting the nucleus of the patient’s own body cells into it, so that the stem cells created in this way will not cause immune rejection in the patient’s body. However, these personalized embryonic stem cells also involve the use of fertilized eggs, which raises ethical issues, and they are not suitable for research or therapeutic use because they have the potential to develop into cancer cells.
Secondly, there are adult stem cells. These are stem cells that can be found in full-grown adults, which are present in each tissue of the body and can only differentiate into cells that make up that specific tissue. The types of adult stem cells we currently know about include bone marrow, fat, and blood stem cells. Unlike embryonic stem cells, adult stem cells have the advantage that their differentiation is stable, so they do not have the potential to become cancerous cells, and they are ethically unproblematic. This makes them more suitable for research and therapeutic use than embryonic stem cells, with bone marrow transplantation being a prime example of a therapeutic use. However, adult stem cells are only present in small amounts in the tissue itself, so the number of stem cells that can be obtained is small, and the types of cells that can be differentiated are limited compared to embryonic stem cells, so while they are good for culturing specific cells, they are not applicable to many fields.
Induced pluripotent stem cells were developed to overcome the problems and limitations of these two types of stem cells. Induced pluripotent stem cells are stem cells created from our own somatic cells by inducing the reverse differentiation of somatic cells, i.e., by applying certain stimuli to them so that they can return to their original stem cell state. Like embryonic stem cells, these stem cells have the advantage of being able to differentiate into any cell in the body, and unlike embryonic stem cells, they do not have ethical issues. However, there is a risk that the factors that are added to the cells for reverse differentiation can cause cancer, as they are part of cancer factors, and they are still in the development stage, which is difficult to apply to clinical use. Therefore, the stem cells that are currently used in research and treatment are mainly adult stem cells, and induced pluripotent stem cells are stem cells that are receiving attention in view of their potential as future cell therapies.
Currently, stem cells are used in some therapeutic fields. The aforementioned bone marrow transplant is a typical example, and stem cell therapy has not been used much outside of bone marrow transplantation. However, researchers are currently working to find treatments for diabetes, rheumatism, Parkinson’s disease, Alzheimer’s disease, cerebral infarction, myocardial infarction, spinal cord repair, and cancer therapy. Stem cells are also being used in basic medical research, such as testing pharmacologic responses with stem cell-derived tissues and organs. Recently, researchers have also been working on combining stem cells with 3D printing technology to create artificial organs with 3D printers, making the process of creating organs for treatment or research more sophisticated and easier.
Stem cell research is rapidly evolving with advances in science and technology. For example, researchers are now utilizing CRISPR-Cas9 gene editing technology to precisely edit the genes of stem cells to increase the potential for treatments for certain diseases. In addition, mini-organs called organoids are being grown from stem cells and used to study the development of human organs or to test the effects of drugs. These studies show that stem cells are becoming more than just cellular therapeutics, they are becoming important tools for understanding human biology and disease.
Like the seeds needed for a tree to grow, stem cells are the source of many of the cells that make up our bodies, and they have the ability to differentiate into different types of cells. Embryonic stem cells and induced pluripotent stem cells can differentiate into almost any cell, while adult stem cells have the ability to differentiate into cells that make up specific tissues. Of the two, adult stem cells are the most studied and used for therapeutic purposes in the clinic because they are safe, with no ethical issues and no potential to cause cancer. Although stem cells have not yet been applied to many practical applications, they are a subject that many people are interested in and studying for their future possibilities.
