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Uses of Embryonic Stem

Cells
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BLASTOCYST
★ The blastocyst is a structure formed in the early embryonic development of mammals.
★ It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently
forms the embryo, and an outer layer of trophoblast cells called the trophectoderm.
★ This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel.
★ In the late blastocyst the trophectoderm is known as the trophoblast.
★ The trophoblast gives rise to the chorion and amnion, the two fetal membranes that
surround the embryo.
★ The placenta derives from the embryonic chorion (the portion of the chorion that develops
villi) and the underlying uterine tissue of the mother.
★ In humans, blastocyst formation begins about five days after fertilization
when a fluid-filled cavity opens up in the morula, the early embryonic stage
of a ball of 16 cells.
★ The blastocyst has a diameter of about 0.1–0.2 mm and comprises 200–300
cells following rapid cleavage (cell division).
★ About seven days after fertilization, the blastocyst undergoes implantation,
embedding into the endometrium of the uterine wall where it will undergo
further developmental processes, including gastrulation.
★ Embedding of the blastocyst into the endometrium requires that it hatches
from the zona pellucida, the egg coat that prevents adherence to the fallopian
tube as the pre-embryo makes its way to the uterus.
EMBRYONIC STEM CELLS

★ Embryonic stem cells (ESCs) are pluripotent stem cells derived from the
inner cell mass of a blastocyst, an early-stage pre-implantation embryo.
★ Human embryos reach the blastocyst stage 4–5 days post fertilization, at
which time they consist of 50–150 cells.
★ Isolating the inner cell mass (embryoblast) using immunosurgery results in
destruction of the blastocyst, a process which raises ethical issues,
including whether or not embryos at the pre-implantation stage have the
same moral considerations as embryos in the post-implantation stage of
development.
★ Researchers are currently focusing heavily on the therapeutic potential of
embryonic stem cells, with clinical use being the goal for many laboratories.
★ Potential uses include the treatment of diabetes and heart disease.
★ The cells are being studied to be used as clinical therapies, models of genetic
disorders, and cellular/DNA repair.
★ These pluripotent stem cells boast special characteristics that often make them
better suited for therapeutic purposes than adult stem cells. It’s helpful to
remember that “adult” stem cells can also refer to those in newborns and
children. The term simply means that the cells are sourced from a human
being after a live birth This makes adult stem cell types non-controversial.
★ ESCs have a normal karyotype, maintain high telomerase activity, and exhibit
remarkable long-term proliferative potential.
USES / APPLICATIONS
1. TISSUE ENGINEERING
● In order to successfully engineer a tissue, the cells used must be able to
perform specific biological functions such as secretion of cytokines,
signaling molecules, interacting with neighboring cells, and producing
an extracellular matrix in the correct organization.
● Embryonic stem cells is one of the sources that are being considered
for the use of tissue engineering.
● It is theorized that if embryonic stem cells can be altered to not evoke
the immune response when implanted into the patient then this would
be a revolutionary step in tissue engineering.
2. CELL REPLACEMENT THERAPY

● Research has focused on differentiating ESCs into a variety of cell types for
eventual use as cell replacement therapies.
● Some of the cell types that have or are currently being developed include
cardiomyocytes, neurons, hepatocytes, bone marrow cells, islet cells and
endothelial cells.
● However, the derivation of such cell types from ESCs is not without obstacles,
therefore research has focused on overcoming these barriers.
● For example, studies are underway to differentiate ESCs into tissue specific
cardiomyocytes and to eradicate their immature properties that distinguish them
from adult cardiomyocytes.
3. CLINICAL POTENTIAL
● Researchers have differentiated ESCs into dopamine-producing cells with the hope
that these neurons could be used in the treatment of Parkinson's disease.
● ESCs have been differentiated to natural killer cells and bone tissue.
● Studies involving ESCs are underway to provide an alternative treatment for diabetes.
For example ESCs have been differentiated into insulin-producing cells, and
researchers at Harvard University were able to produce large quantities of pancreatic
beta cells from ESCs.
● An article published in the European Heart Journal describes a translational process of
generating human embryonic stem cell-derived cardiac progenitor cells to be used in
clinical trials of patients with severe heart failure.
4. DRUG DISCOVERY
● Besides becoming an important alternative to organ transplants, ESCs are also being used
in the field of toxicology, and as cellular screens to uncover new chemical entities that
can be developed as small-molecule drugs.
● Studies have shown that cardiomyocytes derived from ESCs are validated in vitro models
to test drug responses and predict toxicity profiles.
● ESC derived cardiomyocytes have been shown to respond to pharmacological stimuli and
hence can be used to assess cardiotoxicity.
● ESC-derived hepatocytes are also useful models that could be used in the preclinical
stages of drug discovery.
● However, the development of hepatocytes from ESCs has proven to be challenging and
this hinders the ability to test drug metabolism.
● Therefore, research has focused on establishing fully functional ESC-derived hepatocytes
with stable phase I and II enzyme activity.
5. REPAIR OF DNA DAMAGE

● Differentiated somatic cells and ES cells use different strategies for dealing with
DNA damage.
● For instance, human foreskin fibroblasts, one type of somatic cell, use non-
homologous end joining (NHEJ), an error prone DNA repair process, as the primary
pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.
6. MODELS OF GENETIC DISORDER

● Several new studies have started to address the concept of modeling genetic disorders
with embryonic stem cells.
● Either by genetically manipulating the cells, or more recently, by deriving diseased
cell lines identified by prenatal genetic diagnosis (PGD), modeling genetic disorders
is something that has been accomplished with stem cells.
● This approach may very well prove valuable at studying disorders such as Fragile-X
syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model
system.

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