Stem cells

Stem cells by Islam Osman Page 1
tem cell is the
mother of all cells ,
it’s a blank
unspecialized
immature cell that
has the capacity of
self-renewal and
differentiated cells regeneration .
Unique features:
stem cell has some properties that
make it different from other cells
Self-renewal : stem cells are
capable of dividing and renewing
themselves for long periods
Differentiation: stem cells are
blank cells that can be transformed
to other types of cells.
Plasticity: the ability of stem cells
from one tissue to generate
specialized cell type of another
tissue, for example hemopoietic
cells may give rise to skeletal,
myocardial and hepatic cells.
Potency: it’s the differentiation
potential of the stem cells and
according to potency stem cells can
be classified.
Classification of stem cells:
stem cells can be calssified
according to potency to
Totipotent: stem cells produced
from fusion of an egg and sperm.
Cells produced by the first few
divisions of the fertilized egg are
also totipotent. These cells can be
differentiated into embryonic and
extra embryonic cell types (e.g.
placenta)
Pluripotent: stem cells derived
from inner cell mass of the
blastocyst and can differentiate
into cells derived from any of the
three germ layers excluding the
placenta.
Multipotent: stem cells that can
produce only cells of closely related
family of cells for example
hematopoietic stem cells can
differentiate into red blood cells.
White blood cells, platelets, etc.. .
Oligopotent: stem cells that can
differentiate to only few cells, for
example lymphoid stem cells.
Bipotent: dual differentiation, for
example oval cells can differentiate
into hepatic and biliary epithelium.
Unipotent: stem cells that can
produce only one cell type …
S

for example muscle stem cells.
stem cells could be classified also
According to their origin into:
Embryonic stem cells: isolated
from the inner cell mass of the
blastocyst of the discarded
embryos after IVF( in vitro
fertilization) or from aborted
embryos ,which has an ethical
debate in different thoughts and
religions as embryos are destroyed
when inner cell mass is taken.
Fetal stem cells: obtained from
aborted fetal gonadal tissue.
Cord blood stem cells: obtained
from the remaining blood in the
umbilical cord after delivery, these
cells contain a big deal of
hemopoietic stem cells.
Adult stem cells: are multipotent
stem cells present in few numbers
in many sites(bone marrow and
niches) of human body.
Embryonic VS Adult stem cells
Embryonic stem cells pluripotent
i.e. can differentiate to all types of
cells. They have unlimited power of
self-renewal .and in comparison to
adult stem cells , embryonic stem
cells are easier to be obtained (by
IVF) or cloning . the main
disadvantages of embryonic stem
cells is the ethical problem about
the way they are obtained and the
danger of immune rejection later
on . Besides embryonic stem cells
can be tumorigenic (develop
teratomes)
on the other hand, adult stem cells
are not tumorigenic or
immunogenic and the way we
obtain them cause no harm.
but they have limited potency and
self-renewal capacity.

Are there other sources of
stem cells ?
the answer was negative till the
emergence of the last few years ,
science have exceeded the classic
limit of stem cells knowledge by
the appearance of two miracles ,
induced pluripotent stem cells
(IPSc) and stimulus triggered
conversion of somatic cells into
pluripotency (STAP) .
Induced pluripotent stem cells
In the year of 2007 , professor
Shinya Yamanaka and his research
team said that aduld defferenitated
cells can be transformed into
pluripotent cells , and they
published their results of
transforming adult human
fibroblasts into pluripotent cells by
defined factors.
the evidence of success of the trial
is the ability of the induced cells to
develop tumors (teratoma) which
is a sure sign of their pluripotency
by the capacity to develop into
ectodermal,mesenchymal,
endodermal derived structures.
Shinya Yamanaka was given
Nobel Prize in physiology for
the year 2012 in grateful to his
promising work .

Stimulus –Triggered Acquisition of pluripotency (STAP)
the newest breakthrough in the field of stem cell research was declared by
the beginning of this year (2014) by the valuable research of Haruko
Obokata .
simply , adult cells like lymphocytes were exposed to strong external
stimulus like transient low PH resulting in plruipotency.
After doing the resarch using lymphoctes , Obokata did it on other cells of
the bdoy and the same results were obtained.

Applications of stem cells
the last two decades have
witnessed a revolution in stem cells
uasge in fighting a lot of disease
and many trials to understand
many diseases ..here, I will try to
give a brief about these
applications.
In the field of basic research:
clarification of complex events that
occur during human development
and understanding molecular basis
of cancer.molecular mechanisms
for gene control. Role of signals in
gene expression and
defferentiation of stem cells .stem
cell theory of cancer.
In the field of biothchnology
(Drugs):
stem cells can provide specific cell
types to test new drugs .that will
reduce animal testing . also stem
cell lines will help in the
development of effective anti-
tumor drugs.
Cell based therpaies:
Regerative therapy for many
diseases like Parkinsonism ,
Alzhimer’s ,spinal cord injury ,
stroke , burns , heart diseases ,
diabetes …
stem cells In gene therapy .
Stem cells in cancer therapy.

Cardio-vascular
applications of stem cells
Cardiovascular disease (CVD),
which includes hypertension,
coronary heart disease, stroke, and
congestive heart failure, has ranked
as the number one cause of death
in the United States every year
since 1900 except 1918, when the
nation struggled with an influenza
epidemic. Nearly 2600 Americans
die of CVD each day, roughly one
person every 34 seconds. Given the
aging of the population and the
relatively dramatic recent increases
in the prevalence of cardiovascular
risk factors such as obesity and
type 2 diabetes, CVD will be a
significant health concern well into
the 21st century.
Cardiovascular disease can deprive
heart tissue of oxygen, thereby
killing cardiac muscle cells
(cardiomyocytes). This loss triggers
a cascade of detrimental events,
including formation of scar tissue,
an overload of blood flow and
pressure capacity, the
overstretching of viable cardiac
cells attempting to sustain cardiac
output, leading to heart failure,
and eventual death. Restoring
damaged heart muscle tissue,
through repair or regeneration, is
therefore a potentially new strategy
to treat heart failure.
The use of embryonic and adult-
derived stem cells for cardiac repair
is an active area of research. A
number of stem cell types,
including embryonic stem (ES)
cells, cardiac stem cells that
naturally reside within the heart,
myoblasts (muscle stem cells),
adult bone marrow-derived cells
including mesenchymal cells (bone
marrow-derived cells that give rise
to tissues such as muscle, bone,
tendons, ligaments, and adipose
tissue), endothelial progenitor cells
(cells that give rise to the
endothelium, the interior lining of
blood vessels), and umbilical cord
blood cells, have been investigated
as possible sources for regenerating
damaged heart tissue. All have
been explored in mouse or rat
models, and some have been tested
in larger animal models, such as
pigs.

A few small studies have also been
carried out in humans, usually in
patients who are undergoing open-
heart surgery. Several of these have
demonstrated that stem cells that
are injected into the circulation or
directly into the injured heart
tissue appear to improve cardiac
function and/or induce the
formation of new capillaries. The
mechanism for this repair remains
controversial, and the stem cells
likely regenerate heart tissue
through several pathways.
However, the stem cell populations
that have been tested in these
experiments vary widely, as do the
conditions of their purification and
application. Although much more
research is needed to assess the
safety and improve the efficacy of
this approach, these preliminary
clinical experiments show how
stem cells may one day be used to
repair damaged heart tissue,
thereby reducing the burden of
cardiovascular disease.

Stem cells in diabetes Milletus
Scientists believe they may have
moved a step closer to a cure for
the type of diabetes that develops
in childhood and usually leads to a
lifetime of insulin injections.
Researchers in California report
that they have reversed the
equivalent of type 1 diabetes in
mice through transplants of stem
cells. Their experiments have
replaced cells in the pancreas
damaged by the disease that are
unable to make insulin.
Without insulin, the body has
difficulty absorbing sugars such as
glucose from the blood. The
disease usually first shows in
childhood or early adulthood and
used to be a killer, but glucose
levels can now be monitored and
regulated with insulin injections.
Scientists have long wanted to try
to replace the damaged ß-cells that
normally produce insulin. This has
been one of the prime targets of
stem cell experiments. But until
now, it has proved difficult, partly
because mature ß-cells do not
readily regenerate.
Writing in the journal Cell Stem
Cell, scientists at the Gladstone
Institutes in San Francisco describe
how they took a step back and
collected skin cells, called
fibroblasts, from laboratory mice.
Then, by treating the fibroblasts
with a unique "cocktail" of
molecules and reprogramming
factors, they transformed the cells
into endoderm-like cells.
Endoderm cells are a type of cell
found in the early embryo, and
which eventually mature into the
body's major organs – including
the pancreas. "Using another
chemical cocktail, we then
transformed these endoderm-like
cells into cells that mimicked early
pancreas-like cells, which we called
PPLCs," said the Gladstone
postdoctoral scholar Ke Li, the
paper's lead author. "Our initial
goal was to see whether we could
coax these PPLCs to mature into
cells that, like ß-cells, respond to

the correct chemical signals and –
most importantly – secrete insulin.
And our initial experiments,
performed in a petri dish, revealed
that they did."
The team then injected these cells
into mice that had been genetically
modified to have high glucose
levels, mimicking the type 1
diabetes condition in humans.
"Importantly, just one week post-
transplant, the animals' glucose
levels started to decrease, gradually
approaching normal levels," said Li.
"And when we removed the
transplanted cells, we saw an
immediate glucose spike, revealing
a direct link between the
transplantation of the PPLCs and
reduced hyperglycemia [high
glucose level]."
Eight weeks after the
transplantation, the scientists
found that the pancreas-like cells
had turned into the real thing –
fully functional insulin-secreting ß-
cells had developed in the mice.
The team says this is proof of
principle, which one day might be
used to cure type 1 diabetes in
humans. "I am particularly excited
about the prospect of translating
these findings to the human
system," said Matthias Hebrok, one
of the study's authors and director
of the UCSF Diabetes Center.
"Most immediately, this technology
in human cells could significantly
advance our understanding of how
inherent defects in ß-cells result in
diabetes, bringing us notably closer
to a much-needed cure.
Stem cells in skin burns
Stem cells may have a promising
role in the treatment of extenxive
burns and lrge ulcer through
providing suffiecent numbers of
epidermal and epithelial cell lines
that can be used in replacing
damged tissues.

Ethical debate about stem cells
Embryoinc stem cells are derived
from the balstocyst which become
distroyed after aspiration of the
inner cell mass.
though many question appear
logically..
Is an embyro a person?
Is it morally accepted to use
embryos for reaserch ?
Is that considered murder?
some people are in favour of the
stem cell and they have their own
motives …
embryoinc stem cells will decrease
human suffering and get rid off a
lot of diseases that hinder human
production ..that is a global human
aim .
embryonic stem cells are taken
from excess IVF that will be
discarede anyway ..so it’s better to
use them.
the other face of the debate is
against stem cells research entirely
and speciallly against embryonic
stem cells ..also they have their
own thoughts about that..
taking the cells from the balstocyst
destroys it ..that’s murder..
embryonic stem cells research will
open the door to reproductive
cloning ..and that will replace the
role of God ..
the emergence of the great
discovery of Shinya Yamanaka and
the STAP technique will put an end
for this debate for sure ..there will
no need to destroy embryos
anymore ..as adult own cells will be
transformed into pluripotency by
usage of some transcription genes
or some stressor factors.
also the religin and politics play an
important role in directioning stem
cell research all over the world..

References :
1-Robert Lanza , Essentials of stem cells , second edition.
2-Stewart Sell , Stem Cells Handbook .
3- Takahashi, Kazutoshi; Yamanaka, Shinya (2006). "Induction of Pluripotent
Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined
Factors". Cell 126 (4): 663–676
4- Obokata, Haruko; et al. (2014-01-30). "Stimulus-triggered fate conversion
of somatic cells into pluripotency". Nature 505 (7485): 641–647.
5- Jain, KK (2002). "Ethical and regulatory aspects of embryonic stem cell
research". Expert opinion on biological therapy 2 (8): 819–26
6- Current Regulation of Human Embryonic Stem Cell Research (2005).
Guidelines for Human Embryonic Stem Cell Research. Washington D.C, The
National Academies Press: 63-80
7- http://en.wikipedia.org/wiki/Main_Page

Stem cells

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