Could Stem Cells Be The Next Breakthrough in Medicine? Iris Cheung

Could Stem Cells be the Next Breakthrough in Medicine? Iris Cheung (Year 12, Gellhorn)

1 INTRODUCTION

Stem cell* therapy has become increasingly advanced and reliable in the fields of scientific research and regenerative medicine in recent years. Growing at a rate of 36% per year the market will expand even more rapidly when a breakthrough treatment for non-communicable diseases or lifestyle factors occurs [1]. Through promoting the repair of dysfunctional, injured or diseased cells and cell rejuvenation, could this cutting-edge therapy serve to be a turning point and game changer in modern medicine, providing hope for untreatable diseases and creating other breakthroughs?

2 WHAT ARE STEM CELLS?

As the name may suggest stem cells are “stems” / sources from which new, different cells can be made. They are undifferentiated cells which can keep dividing to give rise to other cell types in a process known as “specialization”. This is what allows it to be useful in regenerative medicine. There are four types of stem cells: totipotent, pluripotent, multipotent and unipotent stem cells. Sources of stem cells include embryonic stem cells, adult stem cells and umbilical cord stem cells.

All humans start out as one cell - a zygote (or a fertilized egg cell). The zygote divides by mitosis to form a blastocyst. Eventually, the cells begin to differentiate, taking on one particular function in a part of the body (differentiation). With the correct stimulus given to the unspecialized cells, some genes can be switched on and become active. Messenger RNA (mRNA) is then made from those active genes only and moves out to the ribosomes where it is read. Appropriate proteins are then made, performing a specific function [2].

Embryonic stem cells are derived from blastocysts which is a stage of pre-implantation embryos that have an inner cell mass. After that, these cells are placed in a culture dish filled with culture medium. These cells are pluripotent because in the end, they are able to differentiate into every cell type in the organism. However, one of the problems with embryonic stem cells is the ethical restrictions related to their use in medical therapies [3].

Somatic or adult stem cells are undifferentiated cells that are found among differentiated cells in the whole body after development. These stem cells enable the healing, growth, and replacement of cells that are lost each day; however they have a restricted range of differentiation options. Among the many, there are the following types:

Mesenchymal stem cells, which are present in many tissues. In bone marrow, these cells differentiate mainly into bone, cartilage, and fat cells. As stem cells, they are an exception because they exhibit pluripotent properties and can specialize in the cells of any germ layer. Neural cells eventually form nerve cells as well as their supporting cells: oligodendrocytes and astrocytes. Haematopoietic stem cells form all kinds of blood cells including: red, white, and platelets. Skin stem cells form, for example, keratinocytes that form a protective layer of skin.[4]

Figure 1: The process of formation of embryonic stem cells [5]

3 A BREAKTHROUGH IN STEM CELL THERAPY – iPS cells

The astonishing turning point in stem cell therapy came in 2006, when the scientists Shinya Yamanaka and Kazutoshi Takahashi discovered the possibility to reprogram multipotent adult stem cells to the pluripotent cells using genetic engineering techniques in adult mouse cells. When this proved to be successful, the procedure was then repeated on humans, where genetically modified harmless viruses were used to provide four genes to carry specific transcription factors into the skin cells and synovial fluid of two individuals. This process produced stem cells without using or harming an embryo; the resulting induced pluripotent stem cells (iPS cells) were able to renew themselves, and there was no risk of rejection if cells from an individual were used to produce their own stem cells [6]. This created many new opportunities for the use of stem cells in medicine as it overcame the

ethical concerns regarding the usage of embryonic tissues as a source of stem cells, although there are still underlying problems such as the risk of iPS cells becoming cancerous [7]; however, overall, the differentiation abilities and “ethical-concerns-free” characteristics of iPS are attractive for present and future science research.

4 STEM CELL USE IN MEDICINE

Many serious medical conditions are a result of the improper differentiation of cells or improper cell division. Currently, stem cell therapy has been used to treat medical conditions such as those where there is a loss, shortage or reduced functioning of certain cell types and even incurable diseases; examples include: Parkinson’s disease, Multiple Sclerosis, Type 1 diabetes, and age-related macular degeneration [8]. Additionally, stem cell research could aid our understanding of stem cell physiology [9]. These benefits provide many new opportunities for discoveries in treating incurable diseases, serving as a big leap forward in medicine.

4.1 Therapy for Incurable Neurodegenerative Diseases and Damaged Nerves Although there are no medical cures for neurodegenerative diseases, scientists have found potential in treating, or even curing neurodegenerative diseases through the use of stem cells during experiments with mouse stem cells. They managed to form dopamine neurons from mouse stem cells; Parkinson’s diseases (a neurodegenerative disease) [10], for example, could potentially be treated/cured with stem cell therapy in the near future using similar techniques.

There are also no medical cures for damaged and destroyed nervous tissues in the brain and spine as of yet, as these nerves do not usually regrow. However, trials were carried out in which neural stem cells were injected into the hippocampal area of the brain of mice and rats with damaged spines. Results have shown that stem cells have successfully grown into working adult nerve cells, where damaged spinal cords have also partly rejoined [11]. This showed the possibility for human treatments using the same technique.

4.2 Type 1 Diabetes Type 1 diabetes is an immunodeficiency disease in which the glucose-sensitive, insulinsecreting cells from islets of Langerhans in the pancreas are destroyed and they stop making insulin [12]. Rather than receiving regular treatments such as insulin injections, stem cell therapy may allow the pancreas cells to function properly again, restoring insulin production, and thereby controlling blood glucose levels. Once again, to achieve this, researchers are currently trialling the cells in animals with diabetes to observe the outcome, and if successful, similar techniques can possibly be performed on humans.

4.3 Stem Cells in Phamacological Testing Stem cells can also be useful in drug testing of new drugs before they enter the market, making sure they are effective enough and safe. This can be done by testing on specific differentiated cells from pluripotent cells and monitoring for undesirable effects. If undesirable effects appear, the drug formulas can be altered until they reach a sufficient

level of effectiveness and safety. In this way, drugs can enter the market without human trials, as trialling on humans can sometimes be risky and unethical [13].

4.4 Stem Cells - a Possible Alternative to Arthroplasty Arthroplasty is a surgical procedure to restore the function of a joint. Osteoarthritis (OA) is the most common chronic joint condition where two bones come together in a joint. The ends of these bones are covered with cartilage but in OA, this cartilage breaks down, which causes the bones within the joint to rub together [14]. Treatment for OA is often arthroplasty. However, as an alternative, stem cell therapy can help treat osteoarthritis or stop the onset of osteoarthritis. This is done by collecting adult multipotent stem cells from fat or bone marrow. Multipotent stem cells are then able to be turned into cartilage, bone, muscle, tendon, ligaments, or fat, depending on the type of tissue that surrounds them [15].

4.5 Tissue Banks Tissue banks have become increasingly popular in recent years, particularly in obstetrics. It is known that the umbilical cord is very rich in mesenchymal stem cells, these cells differentiate mainly into the bone, cartilage, and fat cells. Mesenchymal stem cells are an exception because they act as pluripotent stem cells and can specialize in the cells of any germ layer. Additionally, a result of its cryopreservation right after birth, its stem cells can be successfully stored, and then later used in therapies that prevent the future lifethreatening diseases of a patient [16].

5 OBSTACLES IN THE FUTURE

Although stem cell therapy has thrived in the last decade, it is not yet fully mature, and there are still challenges and areas of concern that need to be overcome in the future. Some of these include:

1.

2.

3.

4. More work needs to be done in order to fully understand the mechanism by which stem cells function during animal models or trials, making sure no mistakes are made in the process when repeated on humans. The efficiency of stem cell-directed differentiation must be improved so that stem cells are more reliable and trustworthy for a regular patient. Transplanting functional, new organs made by stem cell therapy would require the creation of millions of working and biologically accurate cooperating cells - hence efficiency and accuracy is needed. Immunological rejection is another major barrier. The immune system may recognize transplanted cells as foreign bodies, triggering an immune reaction resulting in transplant or cell rejection. This is something that needs to be overcome moving forwards [17]. One of the most obvious concerns with stem cell therapy is the ethical issues regarding the use of embryos. There are fewer ethical issues associated with adult stem cells and induced pluripotent stem cells.

Though there are still obstacles to overcome, through many decades of experiments, the potentials of stem cells are unquestionable. The field is making immense advances each day and the influence of stem cells in regenerative medicine is truly incredible.

Currently, untreatable neurodegenerative diseases have the possibility of becoming treatable with stem cell therapy, developments are being made in therapeutic cloning involving stem cells, and there is potential in induced pluripotent stem cells, cell rejuvenation and haematopoietic transplantation. With stem cell therapy and all its regenerative benefits, there is greater potential than ever in history to better, and prolong human life. I believe stem cells really could be the next breakthrough in medicine.

Figure 2: Stem cell therapy research [18]

GLOSSARY

Stem cell: Stem cells are human cells that start off the same and are able to develop into many different cell types [19]. Totipotent: can give rise to any cell type found in an embryo as well as extra-embryonic cells (placenta) [20]. Pluripotent: can give rise to all cell types of the body (but not the placenta); capable of differentiation into any cell within the body, hence able to give rise to cells from any of the three major tissue lineages: ectoderm, mesoderm, and endoderm [21].

Multipotent:can develop into a limited number of cell types in a particular lineage [22]. Unipotent: characterized by the narrowest differentiation capabilities and a special property of dividing repeatedly These cells are only able to form one cell type [23]. Adult stem cells (somatic stem cells): undifferentiated cells found among the normal differentiated cells in a tissue or organ that can differentiate when needed to produce any one of the major cell types found in that particular tissue or organ. Embryonic stem cells: the undifferentiated cells of the early human embryo with the potential to develop into many different types of specialized cells [24]. Blastocyst: an early embryo consisting of a hollow ball of cells with an inner cell mass of pluripotent cells that will eventually form a new organism.

BIBLIOGRAPHY

[1] https://www.weforum.org/agenda/2020/01/how-will-stem-cells-impact-the-futureof-medicine/ [2] https://www.healthline.com/health/stem-cell-research [3,4] https://stemcells.nih.gov/glossary.htm [5] https://www.pinterest.com/pin/685110162046564907/ [6] https://stemcellres.biomedcentral.com/articles/10.1186/scrt37 [7] https://www.technologynetworks.com/cell-science/articles/cell-potency-totipotentvs-pluripotent-vs-multipotent-stem-cells-303218 [8] https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1165-5 [9] https://dev.biologists.org/content/140/12/2457 [10]https://www.hopkinsmedicine.org/stem_cell_research/safety_ethics/are_induced_ pluripotent_stem_cells_safe_yet.html [11,12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264671/ [13] https://www.medicalnewstoday.com/articles/324472 [14]https://www.omicsonline.org/open-access/stem-cell-approaches-for-treatment-ofneurodegenerative-diseases-2167-065X.1000126.php?aid=32555 [15] https://kidshealth.org/en/parents/other-diseases.html [16]https://www.labiotech.eu/in-depth/animal-testing-stem-cells/ [17] https://www.healthline.com/health/osteoarthritis [18] https://www.pinterest.com/pin/685110162046564907/ [18] https://myhealth.alberta.ca/Alberta/Pages/stem-cell-treatment-for-osteoarthritis. aspx [19] https://www.mazecordblood.com/why-bank-cord-blood/what-is-cord-tissue/ [20,21] https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1165-5#refCR107 [22] https://www.technologynetworks.com/cell-science/articles/cell-potency-totipotentvs-pluripotent-vs-multipotent-stem-cells-303218 [23] https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1165-5