Apr 5, 2019 in Science

The Embryonic Stem Cells

Introduction

Stem cells have attracted a great interest of both scientists and the general public, not only by the fact that may be the key to magical healing of the age-related diseases of the heart but also by the fact that their direct use in medicine looks very attractive. Experts in the field of cell technology create the latest techniques and related apparatus for obtaining stem cells not only from bone marrow tissue, but also from peripheral blood, placenta, and umbilical cord blood. Clinical practice shows a high therapeutic efficacy of their use in a variety of profiles, and in practical medicine, namely for treating cardiovascular diseases, diseases of the liver, digestive system, blood system, musculoskeletal system, nervous system, psychiatric, renal, male and female reproductive organs, and others. This paper aims to explore the medical value of the embryonic stem cells and the high therapeutic efficacy of their use in a variety of profiles.

General Information 

The embryonic stem cells are undifferentiated cells derived from an early embryo. They can maintain a long-term replication and transform into a variety of types of differentiated cells. Stem cells serve as a constant source of new cells. In transferring to another early embryo, they may be combined with the inner cell mass of the embryo and included in the development process, giving chimeric animals. Thus, the embryonic stem cells can be among the germ-line cells. In theory, these cells could provide an inexhaustible source of cells for transplantation. Totipotent stem cells that have the ability to generate all types of tissue play a crucial role in the development of the human body providing raw material for the development of all organs and tissues of the embryonic and extra-embryonic tissues. Nowadays, cord blood banking has become popular in the Middle East, particularly in the UAE. This new method uses frozen blood to treat diseases such as blood disorders, cancers, and immune deficiencies. 

It is believed that stem cells are determined by two properties - the ability for sustained self-renewal and pluripotency without aging and the ability to differentiate into one or a plurality of specialized cell types. They are found in various “compartments” of the body, such as bone marrow, liver, brain and skin to provide a mechanism for maintaining the fabric, its growth and regeneration. Many studies assert that these cells may be taken from the patient differentiated in a laboratory and grafted to the same patient for tissue regeneration, which resolves the problem of immune rejection. However, some types of stem cells have a low frequency of occurrence, the difficulty in accessing their location and allocation of limited development potential and poor growth in cell culture. These properties can make them useless for constructing tissues, where cells represent more adequate resources. Embryonic stem cells are an ideal system for the targeting of mutations in the genome of mammals.

Primary cultures of these cells are prepared from cells of the blastocyst (inner cell mass) or primordial germ cells of early post-implantation embryos that can be repeatedly frozen and thawed without loss of the ability to differentiate. Many findings reveal that the ability to conduct a relevant selection of mutant clones or transgenic PGCs and only then to use them as the cell vectors has been widely used in genetic modeling. In the modern genetic medicine, rather than take animals for selection scientists are using well-developed methods for somatic cell genetics.

The Origin of Embryonic Stem Cells

While searching to discover the origin of embryonic stem cells, the scientists tried to find answers to the following questions. What is the origin of hematopoietic stem cells of an adult organism? Is it a single cell line or ontogenetic development that is the re-formation of blood stem cells from the tissue more primitive predecessors? Details of these questions are studied in the blood system of mice. For the first time, stem cells are found in the yolk sac of 7-8-day-old embryos. In 10-day embryo cells appear in the blood and liver. The final content is continuously growing: from the 12th day of the 18th day of fetal life the number of cells in the liver is increased from 75 to 1,500. Stem cells reproduce by dividing, like the rest of the cells. Unlike stem cells that they can divide without limit, mature cells typically have a limited number of division cycles. During stem cell maturation, they go through several stages. As a result, the body has a series of stem cell populations of varying degrees of ripeness. In the normal state, the more mature a cell is, the less likely that it will be able to turn into other cell types. Lee and Wu demonstrates conceptual basis of reporter gene imaging:  

Human stem cells are undifferentiated cellular elements with the properties of self-renewal and differentiation. The term “stem cell” was introduced in 1908 by the Russian hematologist Maksimov. Human stem cells can be classified according to their differentiating potential. Firstly, totipotent cells are capable of forming all embryonic and extra-embryonic cell types. Secondly, pluripotent cells capable of forming all cell types of the embryo. These include embryonic stem cells, primary germ cell and embryonic carcinomas. Other types of stem cells are localized in the mature adult tissues (i.e. adult stem cells) and are referred to adults or by regional tissue stem cells. However, in recent years, scientists have increasingly used classification of stem cell sources for their selection: embryonic, fetal (isolated from abortion material), and the stem cells of the adult organism.

The first application of cord blood stem cells as an alternative to bone marrow transplant took place in 1988 in Paris when a child with Fanconi anemia received a transplant of stem cells derived from umbilical cord of his blood sister. From this moment all over the world - first in the USA and then in Europe cord blood banks were set up and hundreds of studies using the therapy of cord blood stem cells have been conducted. 

 

Differentiation of Embryonic Stem Cells

When receiving the signal from outside, the stem cells are able to differentiate into different types of cells and tissues. In any organism, these signals occur naturally, but they can be created artificially in the laboratory. Embryonic stem cells can be differentiated into three different tissue types: endoderm, which gives rise to internal organs, mesoderm (connective tissue, muscles, circulatory system and bone) and the ectoderm (skin, sensory organs, and nerve cells). Due to this ability to differentiate into different types of tissues, these cells are called multipotent. In case the suspension of embryonic stem cells remains in a liquid medium, they will come together to form embryo like structure and to differentiate spontaneously.

Somatic cells are also capable of differentiating but they are  more limited than embryonic ones. Somatic cells of the same type are capable of giving rise to other cell types. This ability is called plasticity. This property makes it possible to apply somatic stem cells and to use in the therapy of patients and repairing damaged tissue. However, the use of somatic stem cells is limited since they are more difficult to differentiate and they care cultured in laboratory conditions worse than embryonic ones. 

In cases of illness or injury, stem cells can be used to restore or replace damaged tissue. Researchers look for the application of this technology for the treatment of particularly significant for human diseases such as Parkinson’s disease, diabetes, spinal cord injuries, muscular dystrophy, Alzheimer's disease, burns, arthritis, loss of vision and hearing, etc. There are other reasons to study stem cells. First, this is a way to get new knowledge about how an organism develops from a single cell, which signals include mechanisms of differentiation and how it happens. It will allow doctors to understand better and possibly prevent fetal malformations. 

Embryonic and Somatic Stem Cells

Currently, one major source of stem cells is embryonic tissue. The vast majority of recent publications devoted to embryonic stem cells are the most promising ones for the development of cellular technologies. Distinctive features of embryonic stem cells are their ability for endless proliferation of symmetric fission in laboratory culture and clonogenic expressed, for example, the ability to form one of the original stem cell lines. To obtain the stem cells, there must be the destruction of embryos, the sources of which are four, and each has its own pros and cons. The least morally problematic method of obtaining embryos is by in vitro fertilization, but many research groups use other methods of obtaining the embryos clinics that practice in vitro fertilization usually use more than one fertilized egg because the first implantation may not be successful and it takes several procedures. As a result, thousands of unclaimed remains of egg can be used to produce stem cells, which is shown on the picture below. 

In addition, there are many other distinctions between stem cells. The most important one is their ability to survive in the laboratory without differentiating. Embryonic stem cells are capable of replacing stem cells from adult organisms. Dudek has reported that stem cells from adult organisms are present in all tissues and are activated by disease or tissue damage; they are more differentiated than embryonic ones. At the same time plasticity hemopoietin stem cells and somatic stem cells are of the huge interest of the public because of their present properties. They differentiate into a limited number of cell types, for example, they have the potential of multi- or unipotent maturation and do not possess the pluripotency. However, it is not known whether the universal somatic stem cells are as important as embryonic, especially in the treatment of Parkinson’s disease and diabetes. It is also noted that to build large numbers of somatic stem cells is much more complicated than the embryonic ones, and there is a fear that the somatic cells lose their potential over time.

The Use of Stem Cells in Medicine: Problems and Perspectives

Perspectives for the use of cellular technology in many areas of medicine, including organ transplantation, drug trials, treatment and recovery of damaged tissues, etc. are very tempting. However, before reaching the full potential of stem cell technologies it is necessary to solve the following problems:

  1. stem cells must be in sufficient quantities;
  2. differentiation of stem cells should be strictly applied and specific;
  3. stem cells should be viable in the recipient;
  4. transplantation should not inflict any harm to the recipient (including immune rejection reaction, and
  5. after transplantation of stem cells they must be able to integrate into the tissue of the recipient.

Many findings assert that conducting stem cell therapy has become a sensation in the treatment of many serious diseases. Success in modern therapy of malignant diseases is largely associated with this rapidly developing area. Stem cells can be used to produce tissues or entire organs or they can be specially adapted for the intended recipient. Cell replacement therapy for Parkinson’s and Alzheimer’s diseases, as well as in many forms of paralysis and previously incurable autoimmune disease is the most important areas of research. Blood stem cell transplantation is an alternative to bone marrow transplantation and in some cases it has benefits (e.g, chemotherapy or autologous radiation injury).

Today, cord blood stem cells from the umbilical cord are used successfully in the treatment of many complex diseases, including the deadly ones. Diseases can be divided into those for which treatment is carried out according to approved methods, as well as those which are carried out in clinical trials. For example, chronic limb ischemia that is characterized by seemingly innocuous term permanent anoxia hiding arms or legs is treated by the embryonic stem cells. This can be observed in atherosclerosis, systemic connective tissue diseases, and so on. In such cases, stem cells can significantly improve blood flow to the extremities - thus saving patients from fatal consequences.

Conclusion

Until it has not become clear what the ability of stem cells is, whether they can be a panacea, in a state of uncertainty, the supporters and the opponents of stem cells use will have enough arguments against each other. Scientific studies give conflicting results, and opponents argue with each other using partial and little proven academic or quasi-scientific arguments. However, the research has demonstrated a high therapeutic efficacy of stem cells’ use in a variety of profiles, practical medicine (cardiovascular diseases, diseases of the liver, digestive system, blood system, musculoskeletal system, nervous system, psychiatric, renal, male and female reproductive organs, and others.

Related essays