top of page

The Promising Field of Stem Cell Research and its Applications

What are stem cells?

Stem cells are unique cells from which new cell types with specific functions can be developed. They are essentially the first cell type of a cell lineage, and they can either become specialized cells via the process of differentiation, or become new stem cells through the process of self-renewal.


As a matter of fact, stem cells are the only cells in the human body with the ability to generate new cell types. For example, stem cells can differentiate to become nerve cells, liver cells, blood cells, cardiac cells and many others.


In order to be classified as a stem cell, there are two criteria that need to be satisfied:


  1. Self-renewal: These cells should be capable of dividing and renewing themselves for long periods of time whilst maintaining its undifferentiated characteristic.

  2. Potency: These cells must be capable of giving rise to more than one type of specialized cell. As you shall see later, embryonic stem cells and induced pluripotent stem cells are pluripotent as they can give rise to any cell in the human body. Another kind of stem cell, adult stem cells, are multipotent as they give rise to a limited number of cell types.

Figure 1: Representation of the two processes stem cells can undergo. When self-renewal occurs, new stem cells are formed. On the other hand, when differentiation takes place, specialized cells such as neurons, red blood cells, muscle cells and adipose cells are formed.


Types of stem cells


Embryonic stem cells (ESCs)

These are undifferentiated blastocyst cells in the human embryo. The blastocyst is a structure in early embryonic development (3 to 5 days old) that contains the inner cell mass (cluster of cells) from which the embryo arises. In short, ESCs are stem cells that can differentiate into all derivatives from the three primary germ layers of an embryo, namely the endoderm, mesoderm and ectoderm.


Generally, endoderm cells develop into the inner lining of organs, whereas mesoderm cells become organs and ectoderm cells form the epidermis, brain neurons and pigment cells in the same way that these germ layers form organs during organogenesis of an embryo.


ESCs are pluripotent as they can develop into more than 200 cell types in the adult human body and have an unlimited capacity of self-renewal. This versatility makes embryonic stem cells suitable candidates for tissue regeneration. There are many controversies surrounding the use of these cells as their use requires the destruction of an embryo (we discuss this further later in the article). What’s more, ESCs still haven’t been largely researched due to the ethical concerns regarding their use and the current research into induced pluripotent stem cells (discussed in the article later).

Figure 2: The three primary germ layers of an embryo and examples of what each of them can form. The endoderm (in the innermost layer) forms the inner lining of organs and tissues. The mesoderm (in the middle layer) forms cells such as muscle cells and red blood cells, whereas the ectoderm (on the outermost layer) forms the epidermis, neural tissue and pigment cells.


Non-embryonic adult stem cells (ASCs)

Also known as somatic cells (meaning non-reproductive cells; anything besides sperm and egg cells), these cells are undifferentiated cells that regenerate damaged tissue or replace dying cells.


They are multipotent, meaning they can only become some specific cell types. Examples of these include hematopoietic stem cells (i.e. can give rise to different blood cells), epithelial stem cells (can give rise to skin cells), mesenchymal stem cells (can develop into skeletal tissue such as cartilage, bone or fat in the bone marrow) or neural stem cells (can differentiate neurons, astrocytes or oligodendrocytes).


As the use of these cells doesn’t potentially have harm to the body the way embryonic stem cells do, their use is less restricted. However, there currently aren’t technologies available for mass replication in culture, so they are found in very small amounts.


Induced pluripotent stem cells (iPSCs)

These are stem cells created by scientists under laboratory conditions. They are created by reprogramming common adult cells (skin or blood cells, for instance) to become stem cells. These cells are pluripotent, meaning they can develop into any cell type. For example, an IPSC can be reprogrammed to form new blood cells to treat leukaemia patients or beta islet cells to help diabetic patients.


As with adult stem cells, there aren’t ethical implications behind their harvesting as it is non-invasive. What’s more, as they are created from the patient’s own tissue, an immune rejection is prevented as these cells are not foreign to the patient’s body. However, it is believed iPSCs have the potential to be converted into embryos, which may possibly lead to an ethical concern.


Currently iPSCs is the stem cell field gaining more attention as they can result in unlimited yield of stem cells. They are normally obtained from skin fibroblasts (i.e. the principal active cell of the connective tissue) and dedifferentiated (meaning that they return to stem cell state) using a cocktail of transcription factors (which are proteins that control the rate of DNA transcription). Once iPSCs are formed through this method, a different cocktail of transcription factors are used to reprogramme and stimulate the stem cell to develop into the desired cell type (e.g. neurons, cardiac cells). However, this method is still to be proven effective in the large scale as when these cells are reprogrammed into new cell types, only a small percentage of the newly created cells develop into functional cells. Taking neurons as an example, usually less than 10% of the created neurons become fully functional as the rest still remain to fully develop. There is even a risk associated with these underdeveloped cells as their pluripotential properties can lead to the development of cancerous tissue. Thus, direct reprogramming is being studied as a more suitable option.


Direct reprogramming also involves a cocktail of transcription factors but in this case, they allow for skin fibroblasts to directly develop into neurons, avoiding the stem cell stage. Even though this doesn’t result in a large yield of functional cells either, the development of cancerous tissue is avoided.


Other possible uses of iPSCs is to model genetic diseases in vitro. As the human genome is the same in all the cells in one’s own body, a fibroblast could be reprogrammed to become a stem cell and then turned into a desired cell. This can be potentially used to treat any disease caused by a genetic mutation. This way, new insights into disease mechanisms can be investigated as well as to find new therapies. Let’s look at the case of Huntington’s disease (autosomal dominant neurodegenerative disease caused by a mutation in the huntingtin protein). As this mutation is present in all the cells of the patient, fibroblasts from these patients can be obtained, dedifferentiated into stem cells and reprogrammed into neurons. This way, an in vitro model of the disease can be made and used to find new therapy options for the patient.



The applications of stem cells

Due to their unique properties, stem cells are currently at the forefront of many research areas, from tissue regeneration to diabetes treatment or even cancer treatment. They are used to understand the essential properties of cells, to select new drugs, how to imitate the body’s natural cell renewal mechanism, and to study causes of birth defects.


According to the Mayo Clinic, stem cells could be used for:


  • Understanding how diseases occur by examining the way stem cells develop into specialized cells or how mutations happen

  • Regenerative medicine by replacing diseased cells by healthy ones

  • Testing the safety and effectiveness of new drugs. For example, muscle cells could be generated to test the effects of a new cardiovascular drug


Certain stem cells have been used by doctors for clinical therapies for more than 50 years. Such applications include hematopoietic stem cell transplantation (bone marrow transplants), where stem cells from the bone marrow, peripheral blood or umbilical cord blood are used to treat conditions such as leukaemia or lymphoma. Other procedures currently in use include skin replacement using hair follicles stem cells.


There exist many possible applications of stem cells for the treatment of different conditions under research. Potential uses include treating life-threatening illnesses (e.g. stroke, cancer, or myocardial infarction), non-fatal medical conditions (e.g. deafness, blindness, Parkinson’s disease, Alzheimer’s disease, learning defects, or arthritis), and other conditions (e.g. baldness, missing teeth, wound healing, or tissue transplants).


Nonetheless, it is still a field that remains under constant research as its full potential has yet to be achieved. And not to mention, as the field expands with new discoveries being made, new questions will soon arise.


Two main areas of stem cell research will now be introduced, namely regenerative medicine and therapeutic cloning.


Regenerative medicine (stem cell therapy)

Regenerative medicine is an interdisciplinary field that focuses on developing methods to repair or replace damaged or diseased cells, organs or tissues in order to restore its normal function. This involves the generation, transplantation and use of stem cells for therapeutic purposes (for the treatment and prevention of disease) such as stimulation of the body's own repair processes, tissue engineering, and the production of artificial organs. This is mainly done by taking stem cells from the human body, culturing them and introducing them back into the body to induce tissue regrowing.


There are many different therapies under study, such as for Alzheimer’s disease, blindness, different types of cancer (e.g. blood, brain tumor, skin, and solid tumours), HIV, Parkinson’s disease, sickle cell anemia, diabetes, and stroke. For instance, to treat blindness, stem cell therapy would involve replacing retinal cells damaged by disease. One of the tested procedures for this involves injecting stem cells on the rear of the eye, where they would replace the damaged retinal cells.


These therapies are facing certain restrictions as the procedure involves a need for invasive harvesting techniques, possible immune rejection, and limited viability.


Therapeutic cloning (somatic cell nuclear transfer)

Against what the term “cloning” may suggest, therapeutic cloning doesn’t involve the creation of an identical copy of an individual (reproductive cloning would result in this instead).


Also known as somatic cell nuclear transfer (SCNT), therapeutic cloning is the production of embryonic stem cells and then using these cells to repair or sometimes even fully replace tissues and organs that have been damaged. This is done using donated stem cells. Nevertheless, do take note that this technique hasn’t been successful in humans yet as it is still under research and there are still issues regarding their use.


In essence, the SCNT procedure involves:

  1. Extracting the nucleus (which holds the genetic material) from an egg

  2. Extracting the nucleus of a somatic cell (i.e. not sex cell) from the patient

  3. Inserting the nucleus from the somatic cell into an egg without a nucleus

  4. Stimulating the egg to divide into the blastocyst stage, whereby the blastocyst’s inner mass is rich in stem cells


Figure 3: The process of somatic cell nuclear transfer. The process first begins with the isolation of an egg cell followed by the removal of its nucleus. The nucleus of a somatic cell is then fused with the denucleated egg cell, and the cell is stimulated to undertake cell division. When it reaches the blastocyst stage, cell division is halted as the blastocyst’s inner mass is rich in stem cells.


The resulting stem cells are pluripotent and don’t have the risk of immunological rejection. In comparison to the other ways of obtaining stem cells, this method offers many advantages. A potential benefit of therapeutic cloning that is currently under investigation is its applications in stem cell transplant. According to the British National Health Service (NHS), there are currently (in 2020) 6000 people on the waiting list for an organ transplant. As organ transplants are scarce due to lack of donated organs, SCNT could allow for a shorter wait to receive a transplant, as new organs could possibly be created in a laboratory. It would also reduce medical concerns regarding immunological rejection. Besides that, it could help to create patient-specific treatments that are perfectly suited to the patient’s condition.


The main issues regarding therapeutic cloning include:

  • Difficulty in finding stem cell donors

  • Difficulty in obtaining and maintaining embryonic stem cells, coupled with the later instability of the egg without a nucleus

  • Possible mutations and contamination within cultured stem cells

  • Ethical concerns as this procedure results in the destruction of embryos and could provide a toolkit for people to attempt the cloning of humans, which is illegal


Organoids

The term “organoid” means “organ-like”. Hence, organoids are “groups of stem cells grown in laboratories that have organised themselves into cellular structures similar to those found in different organs”. By culturing organ-specific stem cells, scientists have been able to create organoids out of small pieces of tissue to generate synthetic livers, kidneys, and even brains!

As these organoids aren’t true organs and they could potentially be produced in large amounts, they can be manipulated more easily in a laboratory. The different applications of these include the study of three-dimensional (3D) cell interaction and arrangement to further understand how organs are formed from these cells, thereby providing valuable information for advanced regenerative medicine research. Not to mention, this strategy may allow researchers to study diseases or conduct drug discovery as it could allow the pre-testing of treatments on organoids before they are used directly on humans during clinical trials.


Organoids for many tissues have yet to be successfully grown, but there are some successful examples including brain organoids that can develop active nerve cells as well as brain regions to study brain development and diseases. Other than that, intestine organoids resembling the intestine lining have been developed. The size of most organoids, however, are small, whereby they range from less than the width of a hair to the size of a pea.

Some drawbacks and challenges of organoids include the difficulty in obtaining human tissue for scientific study due to the ethical concerns associated with that. In addition to that, most organoids only contain a few of the many cell types in a real organ. Thus, in order to truly recreate an organ, scientists would need to integrate different cells and systems into an organoid.


Dedifferentiation

Dedifferentiation is “a biological phenomenon whereby cells regress from a specialized function to a simpler state reminiscent of stem cells”. This is very promising for researchers as it could further explain cell development and disease, alter plasticity of the differentiated stage of cells (cell plasticity is “ability of some cells to take on the characteristics of other cells in an organism”), and be utilized in regenerative medicine. There is evidence of dedifferentiation at the levels of gene (i.e. changes in gene expression to a progenitor profile), protein (as seen in the up-regulation and down-regulation of cell-related protein), morphology (i.e. cells smaller in size and with less organelles) and function (as these cells are able to proliferate and differentiate again).


Concerns and controversies regarding the use of stem cells

The main ethical concern with the use of stem cells lies in the way embryonic stem cells are utilized. As these procedures result in the death of the embryos, a moral debate arises - should an embryo be treated as a person?


Another concern involves the creation of pluripotent stem cell-derived gametes (i.e. egg or sperm cells). A novel procedure called in vitro gametogenesis (IVG) involves the creation of egg cells from liver cells, blood cells, or other types of cells. By reverse engineering any cell to become an induced pluripotent stem cell (iPSC), this could become a reality. This can be seen as a great advance in assisted reproduction (treatments to result in a pregnancy without sexual intercourse, commonly used to treat infertility), but it can also raise moral questions as to whether these cells could potentially result in a genetically modified individual with special capabilities. Even more, how would the number of embryos a person can create be limited?


Meanwhile, as it is a relatively novel area of research that requires a very specialized and individual treatment, the costs for these procedures are very high, ranging from $5000 to $50,000 per procedure.


With those in mind, there are strong regulations in place, and they must be constantly reviewed and enforced.


Stem cell tourism

Stem cell tourism is a growing trend that involves the payment of large sums of money by patients to private clinics for treatments with often unproven stem cell therapies. Patients seeking novel therapies when conventional medicine hasn’t been able to treat a condition usually frequent this service.


However, as these treatments are still being tested, their effectiveness and safety can’t be assured. As a matter of fact, some experts have even accused these clinics of “financial exploitation”.


Why are stem cells becoming so important nowadays?

Stem cells promise to revolutionize the way medicine is practiced, from treating diseases like cancer, diabetes, Parkinson’s disease and blindness to regenerating organs and tissues. In fact, not only are they being investigated for uses in humans, but also to rescue endangered species.


Nonetheless, all these theories are still under research and require strong ethical guidelines regulating their use. Other therapies to substitute stem cell therapies such as genetic therapies are also under research.


Extra learning resources for you


Author: Covadonga Piquero Lanciego, BSc Biological and Biomedical Sciences

תגובה אחת


חבר/ה לא ידוע/ה
19 באפר׳ 2022

Another factor to consider is how readily accessible treatment locations that offer stem cell therapy. In developed nations, such as the United States, stem cell therapy costs are lower due to experience and tools being more readily available.

לייק
bottom of page