Download Written by: Allison Wilson Allison Wilson is a senior Biomedical

Written by: Allison Wilson
Allison Wilson is a senior Biomedical Engineering major. In her spare time she
enjoys snowboarding, but hopes to never have to use stem cell therapies on her
own snowboarding injuries.
Keywords: stem cells, pluripotent, Parkinson’s, regeneration
Suggested Media: https://www.youtube.com/watch?v=2-3J6JGN-_Y
Abstract: Stem cells are on the forefront of research for the regeneration of
tissues and organs. The different types of stem cells originate from different
sources, some of which are more controversial than others. While stem cells hold
immense potential for medical success, there are current problems that
engineers must overcome before they can be accessible to patients worldwide.
Stem Cells: Nature’s Own Reset Buttons
“I understand that many have ethical and moral reservations about stem cell
research, but for the same reason I describe myself as pro-life, I embrace
embryonic stem cell research because I believe being pro-life is not only caring
for the unborn but also caring for the living.”- Orrin Hatch, from an interview with
CBS on July 23, 2006.
Stem cells are a topic that has ignited heated debates between a plethora
of activist groups since they were proven to exist by Drs. Till and McCulloch in
1961 [1]. The technological advancements that have coupled the research on
stem cells have led to an explosion of findings, many of which that have given
various scientists the conclusion that stem cells can be the answer to all of our
problems- the cure-all of virtually any disease and disorder that is put in front of
us. These discoveries have not all been received with open arms, however.
Many of the mechanisms of obtaining the stem cells, such as cultivation from
animals and embryos, are seen as horrendously unethical. Some may even go
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as far as to stay stem cells are sacrilegious, for it is no one but Gods right to
determine the growth of an organ or even an entire being.
No one can deny the medical potential that stem cells contain, as there
already has been remarkable progress over the past 50 years. However,
regardless of what accomplishments are made, there will be lines drawn and
sides taken. There exist a multitude of possible sides to take, as can be seen by
Orrin Hatch’s statement that pulls from many shades in the spectrum. It is up to
the modern scientists and engineers to push the envelope without knocking
anything valuable over.
What actually are stem cells?
Stem cells are self-replicating cells that have not yet differentiated, or
transformed into the cells that make up the tissues that comprise the body [2].
These cells hold the possibility to turn into muscle cells, red blood cells, brain
cells- they are the chameleons of the human body. Unlike the chameleon,
however, once stem cells undergo the process of differentiation they embody the
characteristics of their nascent form and not just the looks.
There are two different types of stem cells that exist naturally in the body:
embryonic stem cells (ES cells) and adult stem cells. As the name suggests, ES
cells are harvested from the inner cell mass during the blastocyst stage of
embryonic development and are totipotent, meaning that they can give rise to
any kind of both somatic and germ cells, as well as those that make up the
placenta [3]. If successfully removed from the blastocyst, the ES cells have the
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potential to self-replicate for an incredibly prolonged amount of time, which can
lead to the creation of cell lines that have become a pivotal component of
research and medical practices. The ES cells differentiate into the three
embryonic germ layers, the ectoderm, endoderm, and mesoderm, and can
therefore be equated to the building blocks of a living creature, at least at a
cellular level. Adult stem cells, on the other hand, are pluripotent, meaning that
they can still differentiate into the various cells that comprise the body, but do not
have the capability of forming a complete complex organism. These cells are
also tissue-specific and are pre-programmed to turn into their specific cell type
[4]. Mitosis, which is the division of one cell into two daughter cells, allows one of
the daughter cells to remain in its pluripotent state while the other daughter cell
can become more specialized. Adult stem cells are critical in the repair and
reformation of all somatic tissues, including skeletal muscle, cartilage, and hair
[5]. A more recent and much more shocking
discovery came in 1995 when a group of scientists
found neurogenic precursor cells located within
tissues found in the central nervous system. This
gave rise to the idea that neurons may be able to
regenerate, which had previously never been
considered [6]. Fig. 1 shows an image of
regenerated neurons and displays how
further outgrowth may be stimulated in the
Fig. 1 Immunoflourescent image of regenerated neurons.
Source: http://cellphys.ubc.ca/faculty/oconnor/
brain cells. This is an incredible leap forward in the progressive march of the
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medical community, as a knowledge of the mechanism of the regeneration of
brain cells could lead to a potential cure for the most debilitating and fatal
neurodegenerative disorders including Parkinson’s and amyotrophic lateral
sclerosis, more commonly known as ALS.
Obviously, patients that currently have degenerative disorders such as the
ones previously mentioned are not able to combat them successfully with their
natural adult stem cells. Additionally, the usage of ES cells is very controversial,
as many people argue that taking cells from a blastocyst is basically taking away
from the life of the unborn child and giving it to those with the purchasing power.
Scientists around the globe have sought out ways to fix both problems
concurrently, and they may have found the solution in induced pluripotent stem
(iPS) cells. iPS cells are cells that have been genetically altered to revert back to
their undifferentiated state [7]. By introducing a gene into the cells DNA in a “cutand-paste” method, the cells become altered and begin to exhibit characteristics
of ES cells, including their morphology, proliferation, and the formation of
teratomas, or small tumors with more than one germ layer. The injection of the
genes into the cell’s DNA allows the cell to virtually go back in time, and the iPS
cells can be harvested for future use without the invasive and possibly
destructive procedure of removing the inner mass of the blastocyst. Fig. 2 shows
just how powerful stem cells can be, and how they have the potential to benefit
all sides of the medical spectrum.
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Fig. 2. The many different pathways that stem cell therapy can take. Source: [2]
Not only do iPS cells hold the possibility of unlocking the secret to the
regeneration of cells all over the body, as can be seen in Fig. 2, but they actually
may be superior to the ES cells they were looking to emulate. Adding a foreign
material to the body can cause a rejection, but since the iPS cells are capable of
being derived in the body of the person requiring the regeneration, the cells are
already familiar and are expected to be accepted with open arms. Additionally,
the rapid multiplication of healthy iPS cells allows them to self-correct, as their
healthy counterparts quickly override the cells that contain mutations, which
makes these cells appear to have a much lesser risk than the ES cells.
Stem cells are the key to success- right?
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Yes, in a way. Let’s take the Parkinson’s disease that was previously
mentioned. Studies have shown that patients with the disease are able to
incorporate the external fetal cells into their brains and successfully replace the
neurons that had previously been destroyed. The alien cells work as soldiers,
both filling the holes that have been created as well as combating the disease, as
the neurons that are created are able to normalize the levels of dopamine in the
brain, which is a key mechanism of cell death that comes from Parkinson’s [8].
The studies, however, have not been able to determine the optimal method for
choosing and isolating the proper cells, and Fig. 3 shows just one group of
scientist’s methods for harvesting the cells to be transplanted into the brain
region most affected by Parkinson’s.
Fig. 3. A diagram of the different possible cell types and methods of growth for stem cells used to combat Parkinson’s
disease. Source: [8].
There are so many possible cells to isolate in so many different ways, and then
comes the mechanisms of keeping them alive until they are needed, and then the
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methods of inserting them into the patient, and so on and so forth. The future of
stem cell research lies in finding the best and most ethical ways to get them to
the patient, as we have already seen their astonishing potential to work as the
cure to end all diseases.
The Dark Side of Stem Cells
While stem cells may seem like the perfect transformation and
regeneration devices, their ability to grow and proliferate rapidly may actually be
the source of great distress for certain individuals. Specifically, a group of
researchers at the Tulane School of Medicine have linked the stem cells that lie
in the adipose (fat) tissues of obese women to an increase in the growth rate of
breast cancer tumors [9]. The adipose-derived stem cells actually surround the
tumor and feed the cancerous cells, causing the tumor to sustain an incredibly
aggressive growth rate. The study found that the fat-tissue stem cells of obese
patients were much more invasive than those with normal body weights, and this
information opens a number of doors for future research, with the possibility of
targeting and killing off the stem cells instead of the tumor itself. This is indeed an
important concept to consider, for if the tumor is removed but some of the
invasive stem cells remain in the body, the potential for both regression of the
tumor as well as the possibility of a metastasis of the malignant cells remains
[10]. Physicians clearly cannot go wild with the injection of stem cells into one’s
body, for the introduction of too many proliferating cells can lead to a rampant
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and uninhibited spread of cell growth, resulting in even more of the population
being struck by the world’s most deadly diseases.
The Future
There has already been an explosion of progress made in the 50 years
since stem cells were first discovered, yet it seems like we have only touched the
tip of the iceberg in determining all of the future use that may come from these
microscopic entities. From fixing any organ in the body to cloning an entire
organism, the possibilities seem endless. However, the knowledge held by
scientists today is not enough to allow free reign of these therapies. They must
find a way to create a successful balance of the rapidly dividing cells: too many
will lead to tumors and two few simply will not be able to get the job done.
Additionally, they must consider the ethical implications of using certain therapy
methods, as the controversial topic has sparked many heated debates between
people all over the world. Currently, the harvesting and insertion of stem cells is
an uncomfortable and invasive process, so scientists must look to find easier
ways of obtaining the same results, which will not only result in less pain for the
particular patient, but will most likely lower the costs and broaden the range of
those who will be able to receive these life saving treatments. Stem cells are the
medicine of the future, but they must be carefully scrutinized under their shiny
façade to ensure the safest and most effective treatments for all of those wishing
to benefit.
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References
[1] Till, J.E., and McCulloch, E.A. A direct measurement of the radiation sensitivity of
normal mouse bone marrow cells. Radiation Res. 14, 213-222 (1961).
[2] Info Center. In Stem Cell Information [World Wide Web site]. Bethesda, MD:
National Institutes of Health, U.S. Department of Health and Human Services, 2010
[cited Friday, November 15, 2013] Available at
http://stemcells.nih.gov/info/Pages/Default.aspx
[3] Rippon, H. J. and Bishop, A. E. (2004), Embryonic stem cells. Cell Proliferation,
37: 23–34. doi: 10.1111/j.1365-2184.2004.00298.x
[4] Sylvester KG, Longaker MT. Stem Cells: Review and Update. Arch Surg.
2004;139(1):93-99. doi:10.1001/archsurg.139.1.93.
[5] Young, H.E. and Black, A.C. Adult Stem Cells. The Anatomical Record Part A.
276A:75-102. 2004.
[6] Gage FH, et al. 1995. Survival and differentiation of adult neuronal progenitor
cells transplanted to the adult brain. Proc Natl Acad Sci USA 92:11879–11883.
[7] S. Yamanaka. A Fresh Look at iPS Cells Cell, Volume 137, Issue 1, 3 April 2009,
Pages 13–17 http://dx.doi.org/10.1016/j.cell.2009.03.034
[8] O. Lindvall et al. Stem cell therapy for human neurodegenerative disorders- how
to make it work. Nature Medicine. 2004; S42-S50.
[9] Tulane University. “Stem cells of obese women promote the growth of breast
tumors, researchers report”. The Washington Post. 11 November 2013.
[10] Breast Cancer Stem Cell Research. National Comprehensive Cancer Network. 3
March 2011. http://www.mcancer.org/research/stem-cells/breast
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