RUNNING HEAD: INDUCED PLURIPOTENT STEM CELLS: HOW MUCH DO WE REALLY KNOW?

2014 CFP Proposal

Stem Cells Translational Medicine






Induced Pluripotent Stem Cells:
How Much Do We Really Know?
Jessica Mecklosky
Northeastern University













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Abstract

As the debate about embryonic stem cell research continues to take criticism from the
government, the newest topic of induced pluripotent stem cells (iPS cells) has flourished. The
field has gotten much of its distinction by advertising that they are the alternative to embryonic
stem cells and could eventually serve as the replacement of embryonic stem cells as a whole.
Though as the research grows, more scientists have been questioning if these iPS cells are truly
the equivalents of the embryonic type and whether the small disparity between them may affect
the research applications or potential medical interventions (Robinton, D., & Daley, G., 2012).
There has been evidence stating that these cells may be responsible for unwanted growths or
epigenetic changes, much of which has been overlooked due to the desire to call these cells the
definite future of stem cell medicine.
In a study by Bao-Yang Hu et al., expectations were that the iPS cells would behave
identically to embryonic stem cells (hESCs) yet they found some striking differences. The group
found that although these iPS cells differentiated to neuroepithelial (NE) cells and neurons after
the same amount of time and through the same transcriptional system as hESCs do, the IPS cells
also resulted in increased variability of desired product, creating an unwanted cell mass (Hu, B.
et al, 2010). As a neuroscience researcher, this information is extremely important. If the clinical
applications of these cells are for potential medical functions, there should seldom be any
variability. Furthermore, another study uncovered the predisposition of teratomas growing in
response to iPS cell-derived secondary neurospheres (free-floating clusters of neural stem cells)
in chimeric mice (Miura, K. et al., 2009; Boston Childrens Hospital, 2014) which is one of the
most alarming outcomes of these cells. Similarly, Athurva Gore et al. (2011) found that in 22
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human induced iPS cells the result was that each had an average of five genetic mutations per
sample, many of which had causative effects of cancers. Many of these iPS cells have been
genetically altered in order to go back to the embryonic state, but with that, there is an
increased ability for these cells to proliferate to malignant transformations, producing cancer
tumors in various cell masses (Baker, D. et al., 2007)
What I hope to accomplish is to propose a grant in order to research the cancer-like
effects of these iPS cells, specifically in regards to these neural cells. This paper will serve as a
review of the current topics and methods available for the iPS cell creation, while also reviewing
the technicalities and issues associated with these arising cells. As of right now, our knowledge
of the chromosomal abnormalities that come into play with cancer research in these iPS cells is
very limited (Pera, M., 2011). My hopes are to address these concerns with the public and
therefore increase the research done on the potential of these cells, as they have many different
positive possibilities for the future. The main goal is to figure out the explicit factors that
differentiate these cells from their embryonic counterparts on the molecular level. Each step of
each experiment that is done will be dissected and watched until a clearer picture is able to be
seen about where the exact distinction is between the iPS cells so that further investigation can
then proceed into forming safer and more useful applications for the neurodegenerative disease
stem cell line discovery.
~
Reflective Note: iPSCs are regular somatic cells that can be genetically manipulated to go back
to its embryonic form; many scientists are using this as an alternative to stem cells as they
seem to have the same possibilities. Although they sound perfect on paper, since they are such a
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new concept there is much research that must be done in order to make sure that these are safe
and make sure that they truly are the more accepted version of ESCs.



















Bibliography

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Hu, B. Y., Weick, J. P., Yu, J., Ma, L. X., Zhang, X. Q., Thomson, J. A., & Zhang, S. C. (2010).
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Miura, K., Okada, Y., Aoi, T., Okada, A., Takahashi, K., Okita, K., ... & Yamanaka, S. (2009).
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Pera, M. F. (2011). Stem cells: The dark side of induced pluripotency. Nature, 471(7336), 46-47.

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"Teratoma |Boston Children's Hospital."Boston Children's Hospital. N.p., n.d. Web. 27 May
2014. <http://www.childrenshospital.org/health-topics/conditions/teratoma>.