Can induced pluripotent stem cells replace embryonic stem cells?

In this blog post, we will look at the ethical controversy surrounding embryonic stem cells and the potential of induced pluripotent stem cells as an alternative.

 

How to cure incurable diseases in humans

Finding a cure for incurable diseases in humans has long been the dream of many medical scientists and biologists. Diseases caused by internal factors such as cancer and genetic disorders are more difficult to treat than diseases caused by external infections. For example, leukemia is a disease caused by abnormal proliferation of white blood cells, and the only known treatment to date is bone marrow transplantation. However, this surgical method has the obstacle of finding a bone marrow donor that is compatible with the patient. However, treatment using embryonic stem cells eliminates this step and prevents immune rejection. Thus, the use of embryonic stem cells for the treatment of intractable diseases has emerged as a revolutionary approach among scientists. However, embryonic stem cell research raises ethical issues because it requires the destruction of embryos at the blastocyst stage. What answer can be given to the question of whether embryonic stem cell research should be permitted?

 

Definition and characteristics of embryonic stem cells

Stem cells are cells that have the ability to differentiate into specific cells and tissues. Among them, cells obtained from human embryos are called embryonic stem cells. These cells can differentiate into almost any type of cell and can be cultured into any type of cell depending on the input. When a fertilized egg, which is a combination of an egg and sperm, undergoes multiple cell divisions and becomes a blastocyst, it is ready to differentiate into an embryo. At this point, the cells inside the blastocyst have the ability to differentiate into cells of all tissues in the human body, and these cells can be extracted to obtain pluripotent cells. These cells have excellent self-renewal capabilities, can be mass-produced, and do not cause immune rejection, so they can be transplanted into other individuals and species. Embryonic stem cell therapy is attracting attention as a way to treat intractable and genetic diseases by replacing damaged tissues and organs. There are actual cases where blind patients have regained their vision without side effects through embryonic stem cell transplantation. Similarly, diseases such as leukemia and diabetes can also be treated by injecting cells cultured outside the body. There seems to be no cell that can replace embryonic stem cells in terms of stability, functionality, and potential.

 

Ethical issues in embryonic stem cell research

Nevertheless, embryonic stem cell research raises serious ethical issues. It is necessary to accurately identify the issues that arise in embryonic stem cell research. First, there are issues arising from the use of embryos. Human embryonic stem cells are, literally, stem cells obtained from embryos. An embryo is a fertilized egg that has developed for up to eight weeks after fertilization. Embryonic stem cells are generally obtained from embryos that are four to five days old after fertilization. During this process, the early embryo is no longer able to differentiate and cannot develop into a human being. Destroying human life in its early embryonic state is unacceptable and raises crucial bioethical issues in embryonic stem cell research. Embryos used for embryonic stem cells are either created through somatic cell cloning or are leftover embryos from fertility treatments.
Those who propose the use of somatic cell-cloned embryos argue that cloned embryos are not normal reproductive cells fertilized by sperm and eggs, and therefore are not alive. However, is this argument convincing? In fact, there are many cases in which somatic cell-cloned embryos have undergone the same developmental process as normal embryos and been born as living beings. The cloned sheep Dolly was created using this method. Therefore, not to mention residual embryos, the use of somatic cell-cloned embryos also involves the destruction of embryos that undergo the process of human development and cannot be free from ethical issues.
There is also an argument that early embryos cannot be considered human beings. The question of when human life begins has been a subject of long debate. Those who hold this view argue that early embryos should be distinguished from later embryos in terms of dignity. However, this argument is also difficult to accept. This is because early embryos contain all the biological information necessary for human life. Even if early embryos do not have a established personality and are unlikely to develop into complete human beings, sacrificing them cannot be justified. Fertilized eggs, fetuses, and embryos are not separate entities, but continuous human life. Therefore, it is unreasonable to define early embryos as less human, and early embryos must also be respected.

 

Concerns about human cloning

The second issue with this research is the concern about human cloning. As mentioned earlier, it is possible to create cloned life using somatic cell cloning embryos. After the successful cloning of Dolly the sheep, reproductive cloning using somatic cell cloned embryos has been attempted on many animals, and the success rate is increasing significantly. Cloned animals tend to die at an early age or suffer from various diseases. However, these problems are being solved through repeated experiments, and at this point, cloning of primates has been successful. Human cloning may not be impossible in the distant future. Although the use of human embryos for purposes other than therapeutic cloning is prohibited, embryonic stem cell research will inevitably contribute to the realization of human cloning. Human cloning raises not only the issue of the violation of human dignity, but also issues that will have a tremendous impact on society, such as the identity of individuals, the commercialization of cloning, and eugenic genetic manipulation. Embryonic stem cell research carries a high risk of leading down this wrong path.

 

The issue of egg harvesting

Other issues surrounding embryonic stem cell research can also be considered. This research requires a large number of eggs. The egg retrieval process can be harmful to women’s health, and issues such as providing sufficient information about egg donation and the sale of eggs may arise. Furthermore, the objectification of women in life science technology can also be considered. In addition, there are many issues that need to be resolved in order to safely utilize embryonic stem cells, such as immune rejection, the possibility of teratoma formation, and unstable differentiation induction.

 

Positions on embryonic stem cell research in Korea and abroad

In Korea, ethical debates on this research heated up in 2004, mainly among the Korean Association for Bioethics, following the announcement of Professor Hwang’s embryonic stem cell research. The Act on Bioethics and Safety, enacted by the government in 2004, includes provisions related to embryonic stem cell research. It stipulates that “embryos shall not be created for purposes other than pregnancy” (Article 13) and that ” “Remaining embryos whose preservation period has expired may be used for research outside the body until the primitive streak appears embryologically, for research on the development of fertility treatment and contraception techniques, for research on the treatment of muscular dystrophy and other rare and intractable diseases designated by the President, and for other research designated by the President after deliberation by the National Bioethics Committee” (Article 17). In other words, limited research using residual embryos is permitted, and human cloning is prohibited, but the use of somatic cell cloned embryos for the treatment of intractable diseases is permitted. South Korea is one of the few countries, including the United Kingdom, that allows research on surplus embryos. However, most developed countries, such as the United States, Japan, Germany, and France, do not allow the creation of somatic cell cloned embryos due to ethical issues and strictly restrict research that requires the destruction of embryos. In the UK, a law was enacted to allow somatic cell cloning research, but ethical controversies have prevented actual research from being conducted in most cases. As such, many developed countries do not legally allow embryonic stem cell research.

 

Alternative to embryonic stem cells: induced pluripotent stem cells

As mentioned earlier, embryonic stem cells have unlimited potential for research. It is unfortunate that ethical issues prevent us from researching this irreplaceable technology. Therefore, induced pluripotent stem cells (iPSCs) have been proposed as a replacement for embryonic stem cells. iPSCs are created by introducing factors that are characteristically expressed in embryonic stem cells into fully differentiated somatic cells and redesigning them. In 2006, Professor Yamanaka’s research team in Japan succeeded in creating cells similar to embryonic stem cells by introducing four genes, Oct4, Sox2, Klf4, and c-Myc, which play an important role in maintaining the totipotency of embryonic stem cells, into mouse and human somatic cells. These cells grew at a rate similar to that of embryonic stem cells and expressed the pluripotency genes found in embryonic stem cells. In other words, these cells, like embryonic stem cells, can develop into all the tissues that make up the human body. For this achievement, Professor Shinya Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012. Since iPSCs convert a patient’s somatic cells into stem cells, they have the same genes as the patient, eliminating the problem of immune rejection and enabling mass production. Above all, induced pluripotent stem cells are significant in that they resolve the ethical issues associated with existing embryonic stem cells, which can only be obtained by destroying embryos.

 

Clinical application and prospects of induced pluripotent stem cells

Induced pluripotent stem cells, which replace embryonic stem cells that inevitably raise many sensitive controversies in clinical applications, are sufficient to suggest a new paradigm. In the early stages, there was a problem of cancer developing during the process of modifying somatic cells by injecting genes through viruses to produce these stem cells. However, over time, technology has been developed to solve this problem by introducing genes using methods other than viruses. In addition, many reprogramming technologies are being actively developed, such as excluding or replacing some of the four genes to induce pluripotency and achieve the same results. Recently, amazing research results have been announced on the reversal of somatic cells into stem cells through simple stimulation without nuclear transfer or genetic manipulation. As such, iPSCs have changed the landscape of stem cell research, and the focus of global research is currently on this area. However, it is expected to take some time before induced pluripotent stem cells can be applied to cell therapy, as the clinical process is time-consuming.

 

Conclusion: The importance of induced pluripotent stem cell research

In the past, there was a clear divide between those for and against embryonic stem cell research, but since the advent of induced pluripotent stem cells, these cells have established themselves as an alternative to embryonic stem cells. With the development of iPSCs, which are attracting worldwide attention, the debate over embryonic stem cell research has become meaningless. Leaving aside embryonic stem cell research, which is unable to move forward due to many obstacles, it seems that the right approach is to focus on induced pluripotent stem cell research, which is the mainstream in the global academic community. In addition, in order to accelerate the realization of cell therapy using induced pluripotent stem cells and to secure national competitiveness in physiological medicine, it will be necessary to establish institutional mechanisms and provide support and interest at the national level.

 

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EuroCreon

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