The Expanding Horizons of Stem Cell Derivation
Sanika Mahajan
Cluster 7: Biomedical Sciences
Mahajan 2
Stem cells are a hotly discussed topic in medicine, due to their growing potential as well
as due to their impending moral and medical hurdles. The derivation and subsequent
culture of stem cells is the first step on the path to their clinical application, and there are
constantly new advancements in the realm of stem cell derivation that aim to optimize the
process as well as minimize ethical ramifications. This paper discusses the implications
of embryonic and adult stem cell derivation and compares and contrasts the two methods,
ultimately revealing the future of stem cell use and applications.
Introduction:
Astonishingly, regenerative ability is not uncommon in species across nearly every
phylum in existence. The neutral evolutionary status of this trait is believed to be the cause of its
disappearance from the phenotypes of several organisms, humans being among those that have
lost the ability to regenerate body parts. Modern medicine’s current solution is solid organ
transplantation, a method of replacing damaged or lost organs by transferring them from one
human to another. While common, organ transplantation is also rife with potential complications,
including rejection and infection of the transplant, and it has no shortage of ethical controversies
regarding the impartial distribution of donations. Thus, science has discovered an alternative that
has the potential to revolutionize organ repair and replacement. Regenerative medicine is an
emerging field devoted to the use of stem cells in repairing organs and body parts, and it has the
potential to avoid the medical complications of organ transplantation as well as sidestep the
ethical issues involved with organ distribution. Potential regenerative stem cells include human
embryonic stem cells (hESCs) and adult or somatic stem cells (ASCs) (Turksen 1). Currently,
hESCs are at the forefront of regenerative medicine and are more prominent than ASCs due to
their ability to differentiate into cells of any tissue. However, recent breakthrough ASC research
has paved the way for a future in which ASCs are just as flexible as hESCs and are able to avoid
the innate moral issues surrounding the use of embryonic stem cells in medicine.
Mahajan 3
Plasticity:
To gain a complete understanding of the distinctions and the overlap between hESCs and
ASCs, it is important to comprehend plasticity. Plasticity is the ability of a cell to differentiate
into specialized cells of a variety of tissues from the three germ layers of the body. The
categories of plasticity are totipotent cells, which can differentiate into any type of cell in the
human body, pluripotent cells, which can differentiate into any type of cell excluding the
placenta, and multipotent cells, which are specialized and can only differentiate into cells of the
same tissue as their source tissue (Howell and Yoder 182). Embryonic stem cells are pluripotent
and are derived from the blastocyst, a structure that emerges 5-7 days after fertilization and
contains an inner cell mass (ICM) from which the embryo later develops (Findikli 159). Adult or
somatic stem cells are generally multipotent and are derived from some types of adult tissue
(Turksen 1). Both categories of stem cells are explored in this report, and the future of both is
discussed.
Human Embryonic Stem Cells (hESCs)
Human embryonic stem cells arise from the ICM during blastocyst development. In order
to isolate hESCs, ICM cells must be cultured in an environment that allows them to remain
undifferentiated for an extended period of time. ICM cells have been isolated by immunological,
mechanical, chemical, or laser-assisted methods. The immunological method, known as
immunosurgery, requires the embryo to be exposed to an enzyme called pronase, animal-based
complement system (a part of the immune system) reagents, and antibodies. This method proves
ineffective for low-quality embryos with smaller ICMs, and embryos isolated through
immunosurgery carry with them the risk of having nonhuman pathogens. Since the use of the
Mahajan 4
enzyme pronase in immunosurgery exposes embryos to bacterial material, a chemical alternative
can be used that does not require this exposure. The chemical method involves the zona
pellucida, the thick membrane covering a mammalian egg before implantation, being removed
using an acidic solution called Tyrode’s solution. However, the acidity of the solution can prove
disastrous for embryos if the procedure is not performed in the optimal conditions and
timeframe. Another method of hESC derivation is laser-assisted and is modeled after the use of a
noncontact diode laser for in vitro fertilization. Laser use may hold the ability to eliminate
xenogeneic material in the derivation of hESCs, allowing the cells to be used for therapeutic
purposes and avoiding the risk of contamination by pathogens from nonhuman species. A new
mechanical isolation method using sharp needles to cut through both the zona pellucida and the
ICM may also avoid the use of animal-derived substances and acidic solutions, thereby shielding
the embryos from xenogeneic pathogens as well as highly acidic environments (Findikli 165).
The necessity for animal-derived products in hESC derivation and culture has long been
an obstacle in the use of embryonic stem cells, and regenerative medicine has not yet been able
to eliminate dependence on potentially mouse embryonic fibroblasts, also known as feeder cells.
This is a hurdle that must be overcome in order for hESCs to develop. The major ethical issues
broached by hESC are also a problem. The culture of embryonic stem cells requires death of the
embryo and raises concerns about the wrongful creation of life for the purpose of its imminent
destruction (168).
Adult Stem Cells (ASCs) and Plasticity:
It is for the aforementioned reasons that adult stem cell research is an area bursting with
potential. Not only do ASC cultures manage to stay within the ethical boundaries that are often
Mahajan 5
breached by hESC cultures, research now also suggests that ASCs may express more plasticity
than previously known. Somatic stem cells were long regarded as strictly multipotent and were
thought to be useful only in replacing their source tissue. However, recent studies have
questioned this belief and they may show that certain organs contain stem cells that are able to
differentiate into unrelated tissue. Although there is controversy surrounding these studies, they
may open the door to a host of medical possibilities. (Turksen 2). There are two models through
which plasticity has been explained, though both are still shrouded in uncertainty and have yet to
be fully unearthed. The first model of plasticity suggests that all stem cells are equal, but
differentiate into separate types of cells based on the conditions in the cell environment. There
are observations that contradict this model (for example, blood stem cells cannot self-renew
when cultured, but neural stem cells are able to remain undifferentiated and grow in culture-this
raises doubts about the equality of all stem cells). However, studies have produced results that
demonstrated the ability of hematopoietic (blood lineage) stem cells to contribute to hepatocytes
(liver cells), myocardial and other muscle cells, and brain cells, as well as the ability of each of
the aforementioned cell types to convert to hematopoietic cells (Turksen 6). The mechanisms by
which stem cells of these tissues can contribute to the repair and restoration of cells from various
other tissues are still unknown and require further study and experimentation.
Induced Pluripotent Stem Cells (iPSCs):
As previously mentioned, there is also a second model of ASC plasticity that contends
that ASCs may be reverted to a pluripotent state by manipulation. This model suggests that it is
possible to use the factors that allow hESCs to be pluripotent in order to manipulate ASCs into
becoming pluripotent once more. This method attempts to turn time back in order to allow ASCs
Mahajan 6
to regain the pluripotency they exercised as embryonic stem cells. In 2006, Takahashi and
Yamanaka converted somatic cells to cells similar to hESCs with pluripotent qualities and coined
them “induced pluripotent stem cells” (iPSCs). These stem cells are able to differentiate into any
type of cell in the human body. The process of creating iPSCs involved using 24 transcription
factors that aid in the maintenance of hESCs, and injecting mixtures of these genes into mouse
fibroblasts to test their efficacy in rendering the cells pluripotent. It was found that only 4
different transcription factors were able to catalyze the growth of colonies similar to hESCs.
Following this experiment, other groups were able to produce iPSCs from human fetal, neonatal
and somatic cells alike. The results have also been proven reproducible among other species such
as rhesus monkeys and murines (Yildirim 11). The discovery of iPSCs can open the door to a
plethora of medical solutions and allow adult stem cells to fill the shoes of embryonic stem cells
without causing the same ethical controversies. However, in the face of these amazing
opportunities, there are also precautions that science must take in order to ensure the quality and
safety of adult stem cells in the future. It must be confirmed that hematopoietic stem cells or
other stem cells that differentiate into tissue other than their own will be able to maintain this
state while the organism lives without changing back (Yildirim 19).
Conclusion:
The field of regenerative medicine on the brink of breakthrough solutions that may
transform the way medicine treats damaged organs, terminal diseases, and more. Although
embryonic stem cells currently face obstacles due to adverse ethical implications and the need
for xenogeneic material in their culture, and adult stem cells are still unable to provide the same
versatility as hESCs in the creation of somatic cells, the field is still in its infancy and its future is
Mahajan 7
bright. If medicine is able to develop iPSCs and optimize derivation of both adult and embryonic
stem cells in order to minimize ethical issues and improve culture, it could lead to a quicker and
more effective treatment for millions of patients, while avoiding the medical and ethical
complications presented by other solutions such as organ transplantation. Humans may have lost
the evolutionary ability to regenerate many of their own body parts long ago, but they are slowly
beginning to find it once more, this time using regenerative medicine as the cure.
Mahajan 8
Works Cited
Howell, J. C., and M. C. Yoder. "Adult Stem Cell Plasticity Defined."NeoReviews 4.7 (2003): n.
pag. Web. 26 July 2015.
Findikli, Necati. "Human Embryonic Stem Cells from Laboratory and Clinical Perspectives." Springer. N.p., 09 Jan. 2012. Web. 26 July 2015.
Turksen, Kursad. Adult Stem Cells. Totowa, NJ: Humana, 2004. Print.
Yildirim, Sibel. "Induced Pluripotent Stem Cells (iPSCs)." Induced Pluripotent Stem Cells. New
York: Springer, 2012. 11-19. Print.