STEM CELLS: TYPES, APPLICATIONS AND WHERE THEY ARE FOUND - NEUROPSYCHOLOGY - 2024

Stem cells are a type of cell that is found naturally in all multicellular living things. They are characterized by the property of differentiating into any type of cell and dividing to produce more stem cells.

This type of cell is very important from before birth, since a few days after joining the two gametes begin to divide and multiply creating stem cells that will specialize and give rise to the different organs and tissues of the embryo's body.

Stem cell illustration

The importance of stem cells lies in their amazing potential to develop and form almost any type of cell. This ability can be used to repair and replenish damaged or destroyed cells.

Currently, the clinical application of stem cells is being investigated in multiple diseases such as Parkinson's, Alzheimer's or some congenital conditions. Furthermore, there are already stem cell-based products that have begun to be used internationally in orthopedic medicine.

Are there stem cells in adults or only in children?

Stem cells still exist in adult individuals, although in less quantity and with less potential than in the embryonic stage.

These stem cells are present in certain structures such as the bone marrow, muscles, and the brain; Thanks to them, damaged cells can be replaced and organs can continue to function normally.

What differences do they have with other types of cells?

In general, it could be said that stem cells have three main properties that differentiate them from other cells:

• They can reproduce for long periods of time.
• They are not specialized.
• They can specialize in any type of cell.

These properties make them potentially beneficial to treat some diseases caused by the wear or degeneration of some cells such as neurodegenrative diseases.

These incredible properties of stem cells were first investigated just 35 years ago, in 1981, when a group of researchers discovered that it was possible to extract stem cells from a mouse embryo.

It was not until 1998 when studies with mice could be extrapolated to humans, when the first stem cells were extracted from human embryos and cultured in vitro to study their function and properties. These stem cells are called embryonic stem cells.

In 2006 another milestone in the history of the study of stem cells occurred, a group of researchers discovered how some adult cells could be genetically reprogrammed to give rise to stem cells that can specialize in some types of cells. This type of stem cell is called an induced pluripotent stem cell (iPS).

Although much progress has been made in stem cell research in these 35 years, more studies are still needed to better understand them and to be able to use them in the creation of new therapies and in the study of human normative development.

Types of stem cells

Stem cells can be broadly categorized according to their level of maturation into induced embryonic, fetal, adult stem cells, and induced pluripotent stem cells.

Also, not all stem cells have the same potential to differentiate into any type of cell. Depending on the type of cells in which stem cells can be differentiated, they can be:

Totipotent (or omnipotent)

Morula, totipotent cell. Source: Pidalka44 They can differentiate into any type of cell. These cells can only be found in the morula (the set of cells that occurs after the union of the two gametes) and, theoretically, in embryos, although it has not yet been achieved that embryonic stem cells develop and create all types of cells.

Pluripotent

Colony of human embryonic stem cells. Source: Public domain

They are the next step for totipotent stem cells and can differentiate into almost any type of cell. Embryonic cell cultures and induced stem cells are pluripotent.

Multipotent

Confocal micrograph of GFP-positive neural precursor cells (green) in the rat olfactory bulb. Source: Oleg Tsupykov They can differentiate into a wide variety of cells, but only those that belong to a group of related cells. For example, multipotent cells in the heart can only differentiate into tissues that make up the heart. These cells can be collected from fetuses.

Oligopotent

Immature myeloid (oligopotent) dendritic cells Source: Josef Neumüller, Sylvia Emanuela Neumüller-Guber, Johannes Huber, Adolf Ellinger and Thomas Wagner They can differentiate into several types of cells, for example to form the same tissue. Adult stem cells are oligopotent.

Unipotent

Hematocytes type of fetal hepatolasts (unipotent stem cells). Source: Department of Histology, Jagiellonian University Medical College They can only differentiate into one type of cell. These stem cells differ from normal adult cells in that they maintain their reproductive property for a long period of time (before differentiating). This type of stem cells can be found for example in some muscles.

Embryonic stem cell

Embryonic stem cells of a mouse. Source: National Science Foundation

Embryonic stem cells are extracted from embryos. Most come from gametes that have been fertilized in vitro and not from naturally pregnant women. In theory, they are totipotent, that is, they can give rise to any type of cells, although at the moment only some types of cells can be cultured in the laboratory.

Once the stem cells are extracted, a culture is performed in which the cells and nutritional material (culture medium) are introduced into a laboratory dish. In culture the cells grow and begin to divide creating a thin layer that extends over the entire surface of the plate.

Fetal stem cells

Fetal stem cell. Source: Teixeira, J., Rueda, BR, and Pru, JK, Uterine Stem cells (September 30, 2008), StemBook, ed. The Stem Cell Research Community, StemBook, doi / 10.3824 / stembook.1.16.1, Fetal stem cells are obtained from fetuses (from the 10th week of gestation). These cells can be found in most tissues of the fetus.

These stem cells are multipotent, that is, they can differentiate into some types of cells that are related, for example, in several similar tissues to form the same organ.

Adult stem cells

Micrograph of an adult stem cell showing typical ultrastructural features. Source: Robert M. Hunt, Creative Commons Attribution

In some adult tissues, such as skin, muscles, intestine, and bone marrow, there are adult stem cells that can proliferate and differentiate into cells of the same tissue to replace dead or damaged cells, so they are oligopoents. Adult stem cells can also be found in umbilical cord blood.

For example, in the bone marrow there are blood stem cells that mature into mature blood cells (red blood cells, white blood cells, or platelets).

Research with these types of cells is well advanced, and transplants of adult stem cells from bone marrow or umbilical cord blood are currently being performed to treat blood diseases such as myelodysplastic and myeloproliferative syndromes.

The therapeutic potential of other adult stem cells such as mesenchymal cells, which produce cells from bone, cartilage and fat, are currently being investigated to treat diseases such as arthritis.

Induced pluripotent stem cells

Induced pluripotent stem cells. Source: Gepstein Laboratory

Induced pluripotent stem cells (iPS) are already specialized adult cells (eg from the skin) that have been genetically reprogrammed in vitro to have the properties of embryonic stem cells.

To reprogram adult cells, they are taken from adults and cultured on a plate, where viruses created in the laboratory with specific genes are inserted to integrate with the cells and modify their genetic information.

Although iPS cells and embryonic cells share many characteristics, they are not entirely the same, these differences are currently being investigated, as well as new procedures to create iPS.

Although more research is needed, iPS cells are already being used to test the effect of some drugs that are in clinical trials and are expected to be useful for transplantation in the near future.

IPS cell transplants are not currently performed because some animal studies have resulted in cancerous formations, possibly due to the technique used to reprogram the cells.

Stem cell cultures

Blastocyst, internally has stem cells. Source: Gnzlndrs

Stem cell cultures are not 100% effective, there are times when cells do not grow or divide. But, when the culture has been effective, groups of stem cells are taken and new populations are created that will continue dividing and begin to differentiate. Stem cells can be frozen and stored at any point in the process.

During cultivation, stem cells can spontaneously group together and specialize in any type of tissue (muscular, nervous…). That they are able to specialize is a sign that the cells are kept in good condition, but ideally the specialization process is controlled by researchers to create specific cell populations.

To control the differentiation of embryonic stem cells, researchers modulate the chemical composition of the culture medium, the square, or the cells themselves by inserting specific genes into it.

Through multiple studies, protocols have been created indicating what parameters must be modified and how to do it to create specific cell cultures.

At the moment embryonic stem cell transplants are not performed in humans because in some studies with animals, it has been observed that they can lead to the development of cancers. Still research is ongoing and they hold great promise for future treatments.

Stem cell treatments

Currently, the clinical use of stem cells most studied and used in practice is the transplantation of blood stem cells (hematopoietic) from the bone marrow or umbilical cord. They are used to treat blood and immune system problems, as well as to renew damaged cells after chemotherapy or radiotherapy treatment.

Every year more than 26,000 people are treated in Europe with a hemetapoietic stem cell transplant every year. The diseases that can currently be treated with a transplant are:

Leukemias and lymphomas

• Acute myelogenous leukemia.
• Acute lymphoblastic leukemia.
• Chronic myelogenous leukemia.
• Chronic lymphoblastic leukemia.
• Juvenile myelomonocytic leukemia.
• Hodgkin lymphoma.
• Non-Hodgkin's lymphoma.

Diseases related to the bone marrow

• Severe aplastic anemia.
• Fanconi anemia.
• Paroxysmal nocturnal hemoglobinuria.
• Pure red blood cell aplasia.
• Congenital thrombocytopenia / amegakaryocytosis.
• Myeloproliferative and myelodysplastic syndrome.
• Multiple myeloma.

Hereditary immune system diseases

• Severe combined immunodeficiency.
• Wiskott-Aldrich syndrome.

Hemoglobinopathies (diseases of the red blood cells)

• Beta thalassemia major.
• Sickle cell disease

Hereditary metabolic diseases

• Krabbe disease.
• Hurler syndrome.
• Adrenoleukodystrophy.
• Metachromatic leukodystrophy.

Other apps

Another application of stem cell transplants are skin grafts. This application is perhaps the oldest since it has been used since before really understanding how stem cells worked.

Skin grafts are usually done only in extreme cases where the person has large areas of the skin damaged, for example from a severe burn.

The first skin graft was carried out in 1970 and since then the technique has been refined, although there is still a long way to go, since currently the grafted skin is unable to develop hair fullicles or sweat glands.

Holoclar

The latest application of stem cells that has been approved in Europe has been Holoclar, a treatment to repair the damage that the cornea may have suffered, whether they are wounds or burns.

The procedure consists of extracting a small portion of limbal cells in good condition, responsible for repairing the cornea, and culturing them in the laboratory until they form a thin corneal layer that can be transplanted into the patient's eye.

Tissue regeneration

Other possible applications of stem cells are being investigated in clinical trials. The main applications found in research are the regeneration of tissues and organs, treatment of injuries, the treatment of cardiovascular diseases and the treatment of brain diseases.

The use of stem cells for the regeneration of tissues and organs is perhaps its most studied application. If organs or tissues are created from stem cells, they can be transplanted to people who need them, in fact, the first kidney with stem cells has already been created and the results are promising.

Cardiovascular diseases

The results of research on the use of stem cells in the treatment of cardiovascular diseases are also very encouraging.

In 2013, a group of researchers from Massachusetts General Hospital (United States) created blood vessels from parts of human stem cells that were implanted in mice and worked properly. Currently the research is ongoing and they are trying to apply it safely to humans.

Brain diseases

The use of stem cells for the treatment of brain diseases such as Parkinson's or Alzheimer's is being studied using embryonic stem cells for their differentiation potential. The results look promising, although the studies are still in a very early stage.

The study of stem cells is not only done to treat diseases, they are also studied to understand the normal development of healthy cells and to better understand some processes such as cell division and differentiation.

References

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4. National Institutes of Health. (March 5, 2015). Stem Cell Information. Obtained from National Institutes of Health.
5. Schöler, HR (2007). The Potential of Stem Cells: An Inventory. In N. Knoepffler, D. Schipanski, & SL Sorgner, Humanbiotechnology as Social Challenge (p. 28). Ashgate Publishing.
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