Stem Cell Project

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STEM CELLS OVERVIEW

Summed up in one sentence; stem cells are cells, which are able to divide and differentiate during
embryonic development. The name “stem cell” comes from the 19 th century and labels the zygote
and the cells of the early embryo. When a sperm fertilizes an egg cell it produces a zygote. An
embryo is formed when the zygote divides into two cells, then four, eight, sixteen and so on. And it is
during these early stages of embryonic development, when cells are capable of dividing and
producing tissue, as well as differentiating. From that come the two key characteristics of stem cells;
they can divide to produce new cells and therefore can be used to grow and repair tissue and replace
damaged cells, and they can differentiate, meaning make different types of cells. They are present in
bone marrow, skin and liver, however, under natural conditions only allow repair in, for example,
brain, kidney and heart. (Allott, A., & Mindorff, D. (2014). Biology: Course companion. Oxford: Oxford
University Press.)

AREAS OF STEM CELLS’ POTENTIAL

A mentioned before, through differentiation, stem cells can produce cells that are able to repair
damaged and ill tissues, therefore they have great potential in multiple areas of medicine and human
treatment, these range from “oncologic therapeutics to manipulation of the immune system
response, the ability to individually tailor treatments to the specific person’s genetic haplotype, and
the possibility of replacing diseased organs and tissue with genetically engineered materials”. Stem
cells also have potential in the underlying pathophysiological mechanisms of various diseases, the
differences in disease manifestation between individuals, toxicological research and the replacement
of some animal testing by in vitro assays. These assays enable new drugs, monoclonal antibodies, and
engineered cell therapies that can search and destroy dangerous metastasizing cancer stem cells. As
mentioned in the quote above, another area which involves stem cells engineering are genetic
diseases, via replacing mutated gene sequences which cause the disease. Also the manipulation of
donor cells, which provides for a wider range of donor material. Furthermore, stem cells have the
potential to cure HIV and AIDS, by mutating viral receptor genes, which prevents blood cell infection.
Furthermore, research has been done into protein therapeutics, and regenerative medicine focusing
testing on engineered tissues from a pathologist’s perspective. Moreover, stem cells are now part of
trials for reversing blindness and type 1 diabetes. Also embryonic stem cells are being trialled for
spinal cord repair and ALS.1,2. In the future, direct reprogramming of cells without the need for stem
cell expansion and transplantation could be possible. (A. T., K. K., T. P., K. W., M. M., & K. F. (2015,
June 8th). Stem Cell Research.
In File:///C:/Users/Admin/Downloads/10.1177/1091581815581423.pdf. Retrieved October 30, 2018.)

INDUCED PLURIPOTENT STEM CELLS AND HUMAN EMBRYONIC STEM CELLS

The topic of using human embryonic stem cells is very controversial because their acquisition
involves the destruction of human embryos. However, “mammalian embryogenesis elaborates
distinct developmental stages in a strict temporal order. Nonetheless, because development is
dictated by epigenetic rather than genetic events, differentiation is, in principle, reversible…”,
enabling the creation of induced pluripotent stem cells. If induced pluripotent stem cells met the
defining criteria for human embryonic stem cells with the important difference that induced
pluripotent stem cells would not have been derived from human embryos (therefore avoiding
controversy). However, it is still not certain whether human induced pluripotent stem cells do not
differ in clinically important ways from embryonic stem cells. In a recent experiment, they proved
that “four factors (OCT4, SOX2, NANOG, and LIN28) are sufficient to reprogram human somatic cells
to pluripotent stem cells that exhibit the essential characteristics of embryonic stem (ES) cells.”,
specifically karyotypes, telomerase activity, cell surface markers and genes that characterize human
embryonic cells. Furthermore, which is the most important ability of embryonic stem cells, induced
pluripotent stem cells are able to differentiate. Therefore, similar to human embryonic stem cells,
human induced pluripotent stem cells should prove useful for studying the development and
function of human tissues, for discovering and testing new drugs, and for transplantation medicine,
in which induced pluripotent stem cell lines should eliminate the immune rejection from the donor.
Furthermore, usage of induced pluripotent stem cells should make it easier to follow the genetic
diversity of the population, as well as cell lines predisposed to specific diseases. All research,
however, emphasizes that before induced pluripotent stem cells can be used, additional research is
needed. (J. Y., M. V., K. S., J. A., J. F., S. T., . . . J. T. (2012, June 29). Induced Pluripotent Stem Cell Lines
Derived From Human Somatic Cells.
In File:///C:/Users/Admin/Downloads/10.1126/science.1151526.pdf. Retrieved October 30, 2018.)

INDUCTION OF PLURIPOTENT STEM CELLS FROM FIBROBLASTS

As mentioned before, the destruction of human embryos faces ethical controversies which prevents
the usage of human embryonic stem cells in medical areas. However, embryonic stem cells are not as
efficient as induced pluripotent stem cells, for example, it is difficult to generate patient-or disease-
specific embryonic stem cells. On the other hand, differentiated human somatic cells can be
reprogramed into a pluripotent state, which allows the creation of patient and disease-specific stem
cells, which is mentioned before.

Induced pluripotent stem cells can be generated from adult human fibroblasts. These induced
pluripotent stem cells (from adult human dermal fibroblasts with the same four factors: Oct3/4,
Sox2, Klf4, and c-Myc) are similar to human embryonic stem cells in “morphology, proliferation,
surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase
activity.” (K. T., K. T., M. O., M. N., T. I., K. T., & S. Y. (2007, November 30). Induction of Pluripotent
Stem Cells from Adult Human Fibroblasts by Defined Factors.
In File:///C:/Users/Admin/Downloads/10.1016/j.cell.2007.11.019.pdf. Retrieved October 30, 2018.)

AREAS OF CLINICAL TRIALS/STEM CELL THERAPIES

Over the last few years, clinical trials involving stem cell therapies emerged, establishing clinical
pathways for new medicine. These early trials concerned replacing damaged tissue and “providing
extracellular factors that can promote endogenous cellular salvage and replenishment.” Clinical trials
are being examined for a number of conditions, including, for example, the use of bone marrow,
hematopoietic (cord blood stem cells) and mesenchymal stem cells in blood and immune disorders
and replacement of cells. Furthermore, these clinical trials also include neural and embryonic stem
cells, which began in early Phase I/II trials.

Areas of clinical trials include:

- Bone marrow, umbilical cord blood, placental and mesenchymal stem cells
- Cardiac repair
- Neurological applications
- Immunological applications
- Genetic blood diseases
- Adipose stem cells
- Endothelial stem cells
- Pancreatic and islet cells
- Neural stem cells
- Limbal stem cells
- Myoblasts
- Hepatocytes
- Pluripotent stem cells

(A. T., R. T., G. L., & D. G. (2011). Clinical trials for stem cell therapies.
In File:///C:/Users/Admin/Downloads/10.1186/1741-7015-9-52.pdf. Retrieved October 30, 2018.)

CONCLUSION

In my opinion, the benefits of stem cell usage heavily outweigh the risks of stem cell therapies.
Embryonic stem cell therapies, although they require the destruction of a human embryo (which is
not even technically “alive” yet), have the potential to save many more lives, however, induced
pluripotent stem cells remove even that concern. The best solution, therefore, appears to lie in
further clinical trials and research into induced pluripotent stem cells, with all their benefits in
“oncologic therapeutics to manipulation of the immune system response, the ability to individually
tailor treatments to the specific person’s genetic haplotype, and the possibility of replacing diseased
organs and tissue with genetically engineered materials”. Another controversial topic, which arises
from the usage of any kind of stem cells, is whether we should really “play with fate” and change
anything about our genetics at all, since it is something we barely understand and is very close to our
“creation”. I agree with this point to a certain degree. In case of, for example, genetic disease or “life
and death” situations, I believe usage of stem cells is justifiable. However, if the usage of stem cells
progressed to, for example, cosmetics, that might not follow our ethical guidelines. (A. T., K. K., T. P.,
K. W., M. M., & K. F. (2015, June 8th). Stem Cell Research.
In File:///C:/Users/Admin/Downloads/10.1177/1091581815581423.pdf. Retrieved October 30, 2018.)

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