Stem cells

Stem cells have remarkable potential to develop into many different cell types in the body during early life and growth. In addition, many tissues operate as a kind of internal repair system, where they are essentially divided infinitely for the regeneration of other cells as long as the person is or is still alive. When the stem cell is divided, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, red blood cell or brain cell.

Stem cells are distinct from other cell types with two important characteristics. First, they are non-specialized cells capable of replenishing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiological or experimental conditions, they can be stimulated to become tissue or organ cells with special functions. In some organs, such as the intestines and bone marrow, stem cells are regularly divided to repair and replace damaged tissue. In other organs, such as the pancreas and heart, stem cells are divided only under special conditions.

Until recently, scientists were working mainly with two types of stem cells from animals and humans: embryonic stem cells and stem cells that were “physical” or “adult”. Scientists discovered ways to derive embryonic stem cells from early mouse embryos more than 30 years ago, in 1981. A detailed study of mouse stem cell biology led to the discovery in 1998 of a method of deriving stem cells from human embryos and growing cells in the laboratory. These cells are called human embryonic stem cells. Embryos used in these studies for reproduction were created through in vitro fertilization procedures. When no longer needed for this purpose, it was donated for research with the informed consent of the donor.

In 2006, researchers achieved another breakthrough by identifying conditions that would allow some genetically specialized adult cells to assume a stem cell-like condition called Induced pluripotent stem cells (iPSCs).

Stem cells are important for living organisms for several reasons. In a fetus ranging from 3 to 5 days old, called ” Blastocyst”, internal cells lead to the formation of the entire body of the organism, including all types of cells and specialized organs such as the heart, lungs, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscles and the brain, separate groups of adult stemcells generate alternatives to cells that are lost due to normal wear, injury or disease.

Due to its unique regeneration capabilities, these cells offer new potential for treating diseases such as diabetes and heart disease. However, there is still a lot of work to be done in laboratories to understand how these cells are used in cell-based therapies to treat diseases, also referred to as regenerative medicine or compensatory therapy.

Laboratory studies of stem cells enable scientists to identify the basic properties of cells and what makes them different from specialized cell types. Scientists are already using these cells in the laboratory to examine new drugs and develop model systems to study natural growth and identify the causes of birth defects.

Research on these cells continues to enhance knowledge about how organisms develop from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas in contemporary biology, but as with many expanding areas of scientific research, stem cell research raises scientific questions as quickly as new discoveries are generated.

What are the unique characteristics of all stem cells?

Stem cells are different from other types of cells in the body:

 All stem cells – regardless of their origin – have three general characteristics: they are able to divide and regenerate themselves for long periods; They can be converted into specialized cell types.

These cells are able to divide and regenerate themselves for long periods. Unlike muscle cells, stem cells may multiply several times, unlike muscle cells, blood cells, or neurons – which are not usually repeated with themselves. Stem cell groups that multiply for months in the laboratory can produce millions of cells.

Scientists are trying to understand two basic characteristics of  cells related to their long-term self-regeneration:

  • Why embryonic cells can multiply for a year or more in the laboratory without discrimination, but most adult stem cells cannot
  • What are the factors in living organisms that normally regulate stem cell proliferation and self-regeneration

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal fetal development or during abnormal cell division that leads to cancer. Such information will also enable scientists to develop embryonic and non-embryonic cells more efficiently in the laboratory.

The specific factors and conditions that allow cells to remain non-specialized are of great importance to scientists. It took scientists many years of experimentation and mistakes to learn to derive cells and maintain them in the laboratory without automatically distinguishing them in certain cell types. For example, it took two decades to learn how to implant human embryonic cells in the laboratory after the development of mouse stem cell conditions. Similarly, scientists must first understand the signs that enable the non-adult stem cell community to reproduce and remain non-specialist before they can grow large numbers of non-specialized adult cells in the laboratory.

Non-specialized stem cells:

One of the basic characteristics of a stem cell is that it does not have any tissue structures that allow it to perform specialized functions. For example, a stem cell cannot work with its neighbors to pump blood through the body (such as myocardial cells), and cannot transport oxygen molecules through the bloodstream (such as red blood cells). However, non-specialized stem cells can lead to specialized cells, including myocardial cells, blood cells, or neurons.

Stem cells can lead to specialized cells. When non-specialized cells lead to the emergence of specialized cells, the process is called differentiation. During differentiation, the cell usually goes through several stages and becomes more specialized at each step. Scientists have just begun to understand the signals inside and outside cells that lead to every step of the differentiation process. Internal signals are controlled by cell genes, interspersed with long chains of DNA, and carry coded instructions for all cellular structures and functions. External signals of cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The reaction of signals during differentiation causes the cell’s DNA to acquire genetic markers that restrict the expression of DNA in the cell and can be transmitted through cell division.

Many questions remain about the differentiation of stem cells. For example, are internal and external signs of cell differentiation similar to all stem cell types? Can specific groups of signals that promote differentiation to certain types of cells be identified? Addressing these questions may lead scientists to find new ways to control the differentiation of stem cells in the laboratory, thus cultivating cells or tissues that can be used for specific purposes such as cell-based therapies or drug screening.

Adult stem cells usually generate the types of tissue cells in which they live. For example, hematopoietic adult stem cells in the bone marrow usually lead to the emergence of many types of blood cells. It is generally accepted that the hematopoietic cell in the bone marrow — called hematopoietic stem cells — cannot lead to completely different tissue cells, such as neurons in the brain. Trials over the past few years have allegedly shown that stem cells from tissue may lead to the emergence of completely different cell types of tissue. This is still a highly controversial area within the research community. This controversy illustrates the challenges of adult stem cell study and suggests that further research using adult cells is necessary to understand its full potential as future treatments.

Embryonic stem cells

Embryonic cells, as the name suggests, are derived from embryos. Most embryonic cells are derived from embryos originating from fertilized eggs in the laboratory – in a laboratory fertilization clinic – and then donated for research purposes with the informed consent of donors and not derived from fertilized eggs in a woman’s body.

How do embryonic stem cells be implanted in the laboratory?

Human embryonic stem cells (HESCs) are created by transferring cells from the pre-implantation embryo to a plastic laboratory container containing nutrient fluid. Cells divide and spread on the surface of the containers. In and out of the container, the inner surface of the vessel is coated with the embryonic rat skin cells that have been particularly processed so as not to divide. This coating layer is called feeding cells. Mouse cells at the bottom of the vessel provide the cells with a surface that can stick to them. Also, nutrient cells release nutrients in the middle of the vessel.

Researchers have now devised ways to develop embryonic cells without rat feeding cells. This is a major scientific advance due to the risk of transmission of viruses or other molecules in mouse cells to human cells.

The embryonic stem cell line generation process is somewhat ineffective, so the lines are not produced every time the cells from the embryonic stage are placed before transplantation in a vegetative dish. However, if the painted cells succeed and split and start multiplying enough to mobilize the dish, they will be gently removed. Repainting or cell transplantation is repeated several times and months. Each cycle of subcell transplantation is referred to as a pathway. Once the cell line is created, the original cells yield millions of embryonic cells. Embryonic cells that have proliferated in cell culture for six months or more are referred to here without differentiation, which is multi-capable, and appear genetically natural as the embryonic stem cell line. At any stage of the process, batches of cells can be frozen and shipped to other laboratories for further testing.

What laboratory tests are used to identify embryonic stem cells?

At various points during the process of generating embryonic stem cell lines, scientists test the cells to see if they show the basic properties that make them embryonic cells. This process is called characterization.

Scientists studying human embryonic cells have not yet agreed on a standard set of tests that measure the basic characteristics of cells. However, laboratories producing human embryonic stem cell lines use several types of tests, including:

Stem cell transplantation for several months: this ensures that the cells are capable of long-term growth and self-regeneration. Scientists examine the vessels through a microscope to see that the cells appear to be healthy and remain undifferentiated.

Using specific techniques to determine the presence of transcription factors usually produced by undifferentiated cells. Two of the most important copying factors are Nanog and Oct4. Transcription factors help turn on and off genes in a timely manner, an important part of cell differentiation and fetal development processes. In this case, Oct4 and Nanog maintain stem cells in an undifferentiated state, capable of self-regeneration.

Use specific techniques to identify specific markers of the cell surface that are usually produced by undifferentiated cells.

Chromosomal examination under a microscope: This method is used to assess whether chromosomes are damaged or if the number of chromosomes changes but does not detect genetic mutations in cells.

Determine whether cells can be redeveloped, or transplanted, after freezing, melting and repainting.

Test whether human embryonic cells are multi-capable: allowing cells to automatically differentiate into cell structure;

 Because the mouse’s immune system is suppressed, injected human cells are not rejected by the mouse’s immune system and scientists can observe the growth and differentiation of human stem cells. Teratomas usually contain a combination of many types of cells that are differentiated or partially differentiated, an indication that embryonic cells are able to divide into multiple cell types.

How are embryonic stem cells stimulated to differentiate?

As long as embryonic cells in cell tissue are grown under appropriate conditions, they can remain undifferentiated (non-specialized). But if cells are allowed to cluster together to form embryonic bodies, they begin to differentiate automatically. This enables them to form muscle cells, neurons, and many other cell types. Although automatic differentiation is a good indicator that embryonic stem cell culture is healthy, this process is not controlled and is therefore an ineffective strategy for producing tissue for specific cell types.

Therefore, to generate tissue of certain types of differentiated cells such as heart muscle cells, blood cells, or neurons, for example – scientists try to control the differentiation of embryonic cells and change the chemical composition of the middle of the tissue as they change the surface of the cell tissue dish, or modify the cells by introducing certain genes.

Through years of experiments, scientists have created some basic protocols or “prescriptions” for the direct differentiation of embryonic cells in certain specific cell types, contributing to the development of medicine and the speed of scientific research.