Stem Cells

What are stem cells?

Stem cells are cells that have the potential to express any one of their genes in their genome. This means that they have the potential to differentiate into any type of cell in the body.

Differentiation of stem cells

Stem cells are, as we have seen, undifferentiated cells that are able to proliferate or turn into specialised cells. The transformation of a stem cell into a differentiated cell is called differentiation.

Single-celled organisms carry out all their essential functions themselves. Although the functions they perform may be adequate, they cannot be efficient in performing all of them. This is because each function requires a different type of cellular structure and machinery.

No one cell can provide the best conditions for all functions. In multicellular organisms, each cell becomes specialised in a variety of ways to perform a particular function, and the adaptations they acquire ensure that they are maximally efficient in their functions.

The specialised cells are the outcome of stem cells’ differentiation. In most multicellular organisms, including humans, all cells are derived from a fertilized egg called the zygote. In the early stage of development, the zygote undergoes multiple mitotic divisions forming a ball of identical cells (morula). As the organism develops and the cells mature, they change the pattern of the genes they express and hence become different from each other.

There are certain genes that are expressed in almost all cells (housekeeping genes). These are genes that encode essential molecules such as enzymes of respiration and enzymes involved in transcription and translation. Other genes are expressed only in specific cells and are turned off in the other cells.

Let’s have a look at the specialised red blood cells and how the process of their differentiation from stem cells increases the amount of oxygen they can carry to other tissues and organs.

Erythrocytes specialisation

Erythrocytes (red blood cells) have specific adaptations to carry out a specific function (as specialised cells), unlike stem cells, which only possess the basic machine work of a cell.

During the process of erythropoiesis, the haematopoietic stem cells differentiate and adopt different shapes and features as they become erythrocytes.

These changes include:

• Loss of their nucleus and mitochondria to create more space for haemoglobin, which is the main oxygen-carrying protein in erythrocytes.

• An increase in the concentration of haemoglobin in the cell increases to ensure maximum oxygen-carrying capacity.

• Adoption of a specific cytoskeleton that gives the erythrocytes a biconcave structure granting them a larger surface area for gas exchange and increased flexibility to travel through narrow blood vessels.

These adaptations improve the ability of the specialised cells to carry out their function. In this particular example, the adaptations in erythrocytes allow them to efficiently pick up oxygen in the lungs, travel through narrow blood vessels and give off their oxygen to tissues and organs in need.

Properties of stem cells

In mature mammals, only a few cells retain the ability to divide and differentiate into specialised cells. After differentiation, most specialised cells lose the ability to proliferate. This leads to an increased risk of permanent damage after an injury, especially in tissues such as the brain and heart.

Stem cells have two main properties:

1. They have a high capacity to differentiate into more specialised cells. This property is referred to as potency. Each stem cell type has a different potency depending on the number of cell lineages it can give way to.

2. They have the ability to self-renew, so they keep producing stem cells.

Types of stem cells

In order to differentiate into a particular cell type, the stem cell needs to transcribe and translate only some specific parts of its DNA and keep the remaining parts turned off.

When becoming specialised, stem cells take on specific features and adaptations. These may include changing the cell structure, membrane proteins, as well as the type or number of the organelles within them. The process of stem cells becoming specialised cells is called cell differentiation.

Terminally differentiated cells cannot proliferate and replace themselves as they have irreversibly lost the ability to undergo mitosis while acquiring specialised adaptations.

Stem cells originate from a variety of sources in mammals. These include:

• Embryonic stem cells: obtained from embryos in their early stages of development.

• Umbilical cord blood stem cells: obtained from umbilical cord blood. They are similar to adult stem cells.

• Placental stem cells: found in the placenta. They have the potential to develop into specific types of cells.

• Adult stem cells: found in tissues of the fetus and throughout adulthood. These cells are specific to a tissue or organ and their roles are maintenance and repair.

There are several types of stem cells, each possessing a different level of potency. These are:

• Totipotent Stem Cells – these have the ability to become any cell in the body. This means they have the capability to form a complete organism. They are only found in the early stage of embryonic development. An example of a totipotent stem cell is the zygote itself.

• Pluripotent Stem Cells – these cells are found in the embryo and can differentiate into almost any cell type. However, they lack the ability to form cells that make up the placenta. Examples of pluripotent stem cells are embryonic stem cells and fetal stem cells.

• Multipotent Stem Cells – these stem cells are found in adults and can differentiate into various cells but are limited in their capacity. They usually develop into cells of a particular type. For instance, red and white blood cells can be formed from multipotent stem cells called haemopoietic stem cells found in the bone marrow

• Unipotent Stem Cells – these cells can only differentiate into one type of cell, hence uni. They are derived from multipotent stem cells and are present in some adult tissues for regenerative purposes.

This image shows the types of stem cells and the potential parts of the body in which they may prove useful.

Uses of stem cells

Stem cells have a wide range of uses in medicine and scientific research. One of the most promising applications of stem cells is in the development of new treatments for diseases and injuries. By replacing or repairing damaged tissues and organs with healthy, functional cells, stem cell therapies have the potential to revolutionize the treatment of conditions such as heart disease, diabetes, and spinal cord injuries.

Stem cells are also used extensively in scientific research to study human development, genetic disorders, and the effects of drugs and other substances on the body. By providing a window into the earliest stages of life, stem cells are helping scientists to better understand how the human body develops and functions, and to develop new treatments for a wide range of diseases and conditions.

Stem cells in research

Stem cells are widely used in research. They can be used to study cellular processes specific to certain types of cells that would be hard to obtain if it weren't for induced pluripotent stem cells (see below).

Stem cells are also useful to research developmental processes, which would be impossible without them due to ethical concerns. For example, research would not be able to fully understand the signalling processes during embryonic development if not for stem cell research, as using human embryos for this purpose would be absolutely unethical and is banned.

Stem cells in medicine

Stem cell therapies have the potential to save lives and improve the quality of life for many people. This is because stem cells can divide into a large variety of differentiated cell types and so can be used to replace those cells which are damaged by injuries or diseases.

The stem cells in the bone marrow, called haematopoietic stem cells, can divide to produce other blood cells (both white and red blood cells). These stem cells are used to treat immune system diseases and illnesses affecting the blood, such as leukaemia.

Severe combined immunodeficiency (SCID) is a genetic disorder that affects both B and T lymphocyte-mediated immune responses. As a result, patients suffering from SCID have a very weak immune system. Their lymphocytes are unable to create enough antibodies or lack the correct ones to fight and defend against the threat of a pathogen. Therefore, those who suffer from SCID are very vulnerable to infections.

Even those infections which are not usually considered to be severe are liable to be life-threatening in SCID patients. SCID can be treated with a bone marrow transplant. This transplant replaces the faulty bone marrow with donor bone marrow that contains stem cells without the defective genes that cause SCID. The healthy bone marrow stem cells then differentiate to produce functional lymphocytes that can then produce the necessary antibodies to fight and defend against pathogens, so the immune system functions normally.

Treatment of other diseases using stem cells

Stem cells can be used to create specialised cells which can treat a range of human diseases and injuries. Some of the uses of stem cell-derived specialised cells are:

• Skeletal muscle cells can be used to treat illnesses such as muscular dystrophy.

• Beta cells of the pancreas can be used to treat Type 1 diabetes.

• Neurons may be used to treat neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases.

• Epidermal skin cells can be used in the treatment of burns and wounds as they form the outer layer of skin which is damaged in these injuries.

• Retina cells of the eye can be transplanted into the eyes of patients with macular degeneration.

Induced pluripotent stem cells (iPS cells)

The process of making iPS cells involves adding specific transcription factors into already specialised cells, which are then ‘reprogrammed’ into pluripotent stem cells. It is in a way the reverse process of the differentiation a stem cell goes through when transforming into a specialised cell.

The specific transcription factors used in this process cause the specialised cells to express genes that are associated with pluripotency. As a result, the iPS cells will have similar characteristics to embryonic stem cells and hence are capable of self-renewal and differentiation into almost any cell in the whole body.

IPS cells play a major role in regenerative medicine. The iPS cells derived from a patient’s own cells can be used to replace damaged cells or create new tissues or possibly even organs. For example, iPS cells can be used to regrown skin grafts for treating burn injuries or replacing damaged neurons in neurodegenerative diseases such as Parkinson’s disease. Since the cells are derived from the patient’s own cells, there will be no concern about the rejection of the cells by the patient’s immune system. Therefore, using IPS cells involves fewer complications and is surrounded by fewer ethical issues than the use of embryonic stem cells.

Embryonic stem cell research raises some ethical issues because it involves obtaining stem cells from embryos created by in vitro fertilisation (IVF). This procedure results in the destruction of an embryo that has the potential to become a fetus if placed in a womb.

Advantages and disadvantages of stem cells

Stem cells have a number of advantages over previous treatment options. However, generating or obtaining stem cells for medical purposes can be costly and even ethically questionable. Research is still ongoing to improve the current stem cell systems and help future patients.

• Disease modelling and drug discovery: stem cells can be developed into systems to study diseases with fewer ethical concerns than animal research and more biological relevance than purely computerised or in vitro research methods.
• Reduced risk of rejection: using a patient's own stem cells or iPS for therapy and transplants can reduce the risk of rejection, as the cells are genetically identical to the patient's own cells.
• Potential for personalized medicine: the future of medicine is personalized. Although as humans our bodies work in similar ways, each of us has slight differences that can make drugs or certain therapies more or less effective. Using the patient's genetic information and stem cells, we will be able to tailor treatment to the specific necessities of a patient, improving their outcome.
• Research into developmental biology: studying stem cells can help researchers understand how cells differentiate and develop into different types of tissue, which can lead to new insights into human development and disease.
• iPS cells have fewer ethical concerns compared to embryonic stem cells, as the latter are obtained through the destruction of human embryos. Stem cell research can also reduce ethical concerns surrounding animal research, although this depends on how and which types of stem cells are used.

Stem cells also have disadvantages, though: the ethical concerns surrounding embryonic stem cells can be solved by using iPCs, but the high cost and complexity of stem cell production and maintenance still make this research and therapeutic technique complicated to use and scale.