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INTRODUCTION

In multicellular organisms, stem
cells are undifferentiated or partially
differentiated cells that can differentiate into
various types of
cells and proliferate indefinitely to produce
more of the same stem cell. They are the
earliest type of cell in a cell lineage. Cell
lineage denotes the developmental history of
a tissue or organ from the fertilized embryo.
They are found in both embryonic and adult
organisms, but they have slightly different
properties in each. They are usually
distinguished from progenitor cells, which
cannot divide indefinitely, and precursor or
blast cells, which are usually committed to
differentiating into one cell type.
The first therapy using stem cells was a bone
marrow transplant performed by French
oncologist Georges Mathé in 1958 on five
workers at the Vinca Nuclear
Institute in Yugoslavia who had been affected
by a criticality accident. The workers all
survived
End of page 1
Properties[edit]
The classical definition of a stem cell requires
that it possesses two properties:
 Self-renewal: the ability to go through
numerous cycles of cell growth and cell
division, known as cell proliferation,
while maintaining the undifferentiated
state.
 Potency: the capacity
to differentiate into specialized cell
types. In the strictest sense, this
requires stem cells to be
either totipotent or pluripotent—to be
able to give rise to any mature cell type,
although multipotent or unipotent prog
enitor cells are sometimes referred to as
stem cells. Apart from this, it is said that
stem cell function is regulated in a
feedback mechanism.
Self-renewal[edit]

Two mechanisms ensure that a stem cell

population is maintained are:
1. Asymmetric cell division: a stem cell divides
into one mother cell, which is identical to the
original stem cell, and another daughter cell,
which is differentiated.
When a stem cell self-renews, it divides and
does not disrupt the undifferentiated state.
This self-renewal demands control of cell
cycle as well as upkeep of multipotency or
pluripotency, which all depends on the stem
cell.
2. Stochastic differentiation: when one stem
cell grows and divides into two differentiated
daughter cells, another stem cell
undergoes mitosis and produces two stem
cells identical to the original.
Stem cells use telomerase, a protein that
restores telomeres, to protect their DNA and
extend their cell division limit Telomerase,
also called terminal transferase, is
a ribonucleoprotein that adds a species-
dependent telomere repeat sequence to
the 3' end of telomeres. A telomere is a region
of repetitive sequences at each end of
the chromosomes of most eukaryotes.
Telomeres protect the end of the chromosome
from DNA damage or from fusion with
neighbouring chromosomes. Telomerase
restores short bits of DNA known
as telomeres, which are otherwise shortened
when a cell divides via mitosis.
In normal circumstances, where telomerase is
absent, if a cell divides recursively, at some
point the progeny reach their Hayflick
limit, which is believed to be between 50 and
70 cell divisions. At the limit the cells become
senescent and cell division stops. Telomerase
allows each offspring to replace the lost bit of
DNA, allowing the cell line to divide without
ever reaching the limit. This same unbounded
growth is a feature of cancerous growth.
 Potency

Cell potency is a cell's ability

to differentiate into other cell types.[1][2]
[3] The more cell types a cell can differentiate
into, the greater its potency. Potency is also
described as the gene activation potential
within a cell, which like a continuum, begins
with totipotency to designate a cell with the
most differentiation
potential, pluripotency, multipotency, oligopote
ncy, and finally unipotency.
Totipotency is the ability of a single cell to
divide and produce all of the differentiated
cells in an organism. Spores and zygotes are
examples of totipotent cells. In the spectrum
of cell potency, totipotency represents the cell
with the greatest differentiation potential,
being able to differentiate into
any embryonic cell, as well as extraembryonic
cells. In contrast, pluripotent cells can only
differentiate into embryonic cells.
It is possible for a fully differentiated cell to
return to a state of totipotency. This
conversion to totipotency is complex, not fully
understood and the subject of recent
research. Stem cells resembling
totipotent blastomeres from 2-cell stage
embryos can arise spontaneously in mouse
embryonic stem cell cultures[9][10] and also
can be induced to arise more frequently in
vitro through down-regulation of
the chromatin assembly activity of CAF-1.
The human development model is one which
can be used to describe how totipotent cells
arise. Human development begins when
a sperm fertilizes an egg and the resulting
fertilized egg creates a single totipotent cell,
a zygote.In the first hours after fertilization,
this zygote divides into identical totipotent
cells, which can later develop into any of the
three germ layers of a human, or into
cytotrophoblast or syncytiotrophoblast cells of
the placenta .After reaching a 16-cell stage,
the totipotent cells of the morula differentiate
into cells that will eventually become either
the blastocyst's Inner cell mass or the
outer trophoblasts. Approximately four days
after fertilization and after several cycles of
cell division, these totipotent cells begin to
specialize. The inner cell mass, the source
of embryonic stem cells, becomes pluripotent.
Research on Caenorhabditis
elegans suggests that multiple mechanisms
including RNA regulation may play a role in
maintaining totipotency at different stages of
development in some species.

In mouse primordial germ cells, genome-wide

reprogramming leading to totipotency involves
erasure of epigenetic imprints.
Reprogramming is facilitated by active DNA  
Pluripotency[edit]
A: Human embryonic stem cells (cell colonies that are not yet differentiated).
B: Nerve cell
Pluripotency[edit

In cell biology, pluripotency refers to a stem

cell that has the potential to differentiate into
any of the three germ layers
endoderm -interior stomach lining,
gastrointestinal tract, the lungs,
mesoderm-muscle, bone, blood, urogenital,
ectoderm- epidermal tissues and nervous
system,
but not into extra-embryonic tissues like the
placenta is differentiate from pluripotent stem
cells. However, cell pluripotency is a
continuum, ranging from the completely
pluripotent cell that can form every cell of the
embryo proper- embryonic stem cells and
Induced pluripotent stem cells to the
incompletely or partially pluripotent cell that
can form cells of all three germ layers but that
may not exhibit all the characteristics of
completely pluripotent cells.
z

Induced pluripotent stem

Induced pluripotency[edit]

Induced pluripotent stem cells are a type of

pluripotent stem cell artificially derived from a
non-pluripotent cell, typically an adult somatic
cell, by inducing a forced expression of
certain genes and transcription factors. These
transcription factors play a key role in
determining the state of these cells and also
highlights the fact that these somatic cells do
preserve the same genetic information as
early embryonic cells. In 2007 induced
pluripotent stem cells were derived from
human dermal fibroblasts using methods
similar to those used for the induction of
mouse cells. These induced cells exhibit
similar traits to those of embryonic stem cells
but do not require the use of embryos. Some
of the similarities between Embryonic stem
cells and induced pluripotent stem cells
include pluripotency, morphology, self-
renewal ability, a trait that implies that they
can divide and replicate indefinitely, and gene
expression
Epigenetic factors are also thought to be
involved in the actual reprogramming of
somatic cells in order to induce pluripotency. It
has been theorized that
certain epigenetic factors might actually work
to clear the original somatic epigenetic marks
in order to acquire the new epigenetic marks
that are part of achieving a pluripotent state.
Chromatin is also reorganized in induced
pluripotent stem cells and becomes like that
found in Embryonic stem cells in that it is less
condensed and therefore more
accessible. Euchromatin modifications are
also common which is also consistent with the
state of euchromatin found in Embryonic stem
cells.
Due to their great similarity to Embryonic stem
cells, induced pluripotent stem cells have
been of great interest to the medical and
research community. Induced pluripotent stem
cells could potentially have the same
therapeutic implications and applications as
Embryonic stem cells but without the
controversial use of embryos in the process, a
topic of great bioethical debate. In fact, the
induced pluripotency of somatic
cells into undifferentiated induced pluripotent
stem cells was originally hailed as the end of
the controversial use of embryonic stem cells.
However, induced pluripotent stem cells were
found to be potentially tumorigenic, and,
despite advances, were never approved for
clinical stage research in the United States.
Setbacks such as low replication rates and
early senescence have also been
encountered when making induced pluripotent
stem cells, hindering their use as Embryonic
stem cell replacement.
Multipotency[edit]
Further information: Progenitor cells

Hematopoietic stem cells are an example of multipotency. When they differentiate into myeloid or lymphoid
progenitor cells, they lose potency and become oligopotent cells with the ability to give rise to all cells of its
lineage
Multipotency describes progenitor cells which
have the gene activation potential to
differentiate discrete cell types. For example,
a multipotent blood stem cell and this cell type
can differentiate itself into several types of
blood cell
like lymphocytes, monocytes, neutrophils,
etc., but it is still ambiguous
whether Haemopoetic stem cells possess the
ability to differentiate into brain cells, bone
cells or other non-blood cell types. human
umbilical cord blood stem cells differentiate
into human neurons. Research is focusing on
converting multipotent cells
into pluripotent cells. Multipotent cells are
found in many, but not all human cell types.
Multipotent cells have been found in cord
blood, adipose tissue, cardiac cells, bone
marrow, and mesenchymal stem cells which
are found in the third molar.
Oligopotency
In biology, oligopotency is the ability
of progenitor cells to differentiate into a
few cell types. It is a degree of potency.
Examples of oligopotent stem cells are the
lymphoid or myeloid stem cells. A lymphoid
cell specifically, can give rise to various blood
cells such as B and T cells, however, not to a
different blood cell type like a red blood cell.
Examples of progenitor cells are vascular
stem cells that have the capacity to become
both endothelial or smooth muscle cells.
Unipotency
In cell biology, a unipotent cell is the concept
that one stem cell has the capacity to
differentiate into only one cell type. It is
currently unclear if true unipotent stem cells
exist. Hepatoblasts, which differentiate
into hepatocytes which constitute most of
the liver or cholangiocytes which are epithelial
cells of the bile duct, are bipotent. A close
synonym for unipotent cell is precursor cell.
 Mouse embryonic stem cells with fluorescent

marker Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer
Embryonic Stem cells

Embryonic stem cells are the cells of the inner

cell mass of a blastocyst, formed prior
to implantation in the uterus. Embryonic stem
cells are pluripotent and give rise during
development to all derivatives of the
three germ layers. they can develop into each
of the more than 200 cell types of the
adult body when given sufficient and
necessary stimulation for a specific cell type.
They do not contribute to the extraembryonic
membranes or to the placenta. By using
human embryonic stem cells to produce
specialized cells like nerve cells or heart cells
in the lab, scientists can gain access to adult
human cells without taking tissue from
patients. They can then study these
specialized adult cells in detail to try to
discern complications of diseases, or to study
cell reactions to proposed new drugs.
MESENCHYMAL STEM CELLS

Mesenchymal stem cells are known to be

multipotent, which can be found in adult
tissues, for example, in the muscle, liver, bone
marrow. Mesenchymal stem cells usually
function as structural support in various
organs as mentioned above, and control the
movement of substances. Mesenchymal stem
cells can differentiate into numerous cell
categories as an illustration of adipocytes,
osteocytes, and chondrocytes, derived by the
mesodermal layer. Where the mesoderm
layer provides an increase to the body’s
skeletal elements, such as relating to the
cartilage or bone. This mechanism helps with
space-filling thus, key for repairing wounds in
adult organisms that have to do with
mesenchymal cells in the dermis, bone, or
muscle. Mesenchymal stem cells are known
to be essential for regenerative medicine.
They are broadly studied in clinical trials.
Since they are easily isolated and obtain high
yield, high plasticity, which makes able to
facilitate inflammation and encourage cell
growth, cell differentiation, and restoring
tissue derived from immunomodulation and
immunosuppression. Mesenchymal stem cell
comes from the bone marrow, which requires
an aggressive procedure when it comes to
isolating the quantity and quality of the
isolated cell, and it varies by how old the
donor. When comparing the rates of
mesenchymal stem cell in the bone marrow
aspirates and bone marrow stroma, the
aspirates tend to have lower rates of
Mesenchymal stem cell than the stroma.
Mesenchymal stem cell are known to be
heterogeneous, and they express a high level
of pluripotent markers when compared to
other types of stem cells, such as embryonic
stem cells.
CELL CYCLE CONTROL
Embryonic stem cells have the ability to divide
indefinitely while keeping their pluripotency,
which is made possible through specialized
mechanisms of cell cycle control. Compared to
proliferating somatic cells, Embryonic stem cells
have unique cell cycle characteristics such as rapid
cell division caused by shortened G1 phase,
absent G0 phase, and modifications in cell cycle
checkpoints which leaves the cells mostly in S
phase at any given time. Embryonic stem cells
rapid division is demonstrated by their short
doubling time, which ranges from 8 to 10 hours,
whereas somatic cells have doubling time of
approximately 20 hours or longer. 
As cells differentiate, these properties change, G1
and G2 phases lengthen, leading to longer cell
division cycles. Since G1 phase is the phase in
which cells have increased sensitivity to
differentiation. Shortened G1 is one of the key
characteristics of embryonic stem cells and plays
an important role in maintaining
undifferentiated phenotype. Although the exact
molecular mechanism remains only partially
understood, several studies have shown insight
on how embryonic stem cells progress through G1
and potentially other phases so rapidly. The cell
cycle is regulated by complex network
of cyclins, cyclin-dependent kinases, cyclin-
dependent kinase inhibitors , pocket proteins of
the retinoblastoma family, and other accessory
factors. In a somatic cell cycle, oscillatory activity
of Cyclin dependent kinase complexes is observed
in sequential action, which controls crucial
regulators of the cell cycle to induce
unidirectional transitions between phases
Stem cell Therapy

Stem cell therapy is the use of stem cells to

treat or prevent a disease or condition. Bone
marrow transplant is a form of stem cell
therapy that has been used for many years
because it has proven to be effective in
clinical trials.
Stem cell implantation may help in
strengthening the left-ventricle of the heart, as
well as retaining the heart tissue to patients
who have suffered from heart attacks in the
past.
Advantages

Stem cell treatments may lower symptoms of

the disease or condition that is being treated.
The lowering of symptoms may allow patients
to reduce the drug intake of the disease or
condition. Stem cell treatment may also
provide knowledge for society to further stem
cell understanding and future treatments.
Disadvantages

Stem cell treatments may

require immunosuppression because of a
requirement for radiation before the transplant
to remove the person's previous cells, or
because the patient's immune system may
target the stem cells. One approach to avoid
the second possibility is to use stem cells from
the same patient who is being treated.
Pluripotency in certain stem cells could also
make it difficult to obtain a specific cell type. It
is also difficult to obtain the exact cell type
needed, because not all cells in a population
differentiate uniformly. Undifferentiated cells
can create tissues other than desired types.
Some stem cells form tumors after
transplantation; pluripotency is linked to tumor
formation especially in embryonic stem cells,
fetal proper stem cells, induced pluripotent
stem cells. Fetal proper stem cells form
tumors despite multipotency.
Telomerase

Stem cells use telomerase, a protein that

restores telomeres, to protect their DNA and
extend their cell division limit Telomerase,
also called terminal transferase, is
a ribonucleoprotein that adds a species-
dependent telomere repeat sequence to
the 3' end of telomeres. A telomere is a region
of repetitive sequences at each end of
the chromosomes of most eukaryotes.
Telomeres protect the end of the chromosome
from DNA damage or from fusion with
neighbouring chromosomes. Telomerase
restores short bits of DNA known
as telomeres, which are otherwise shortened
when a cell divides via mitosis. In normal
circumstances, where telomerase is absent, if
a cell divides recursively, at some point the
progeny reach their Hayflick limit, which is
believed to be between 50 and 70 cell
divisions. At the limit the cells become
senescent and cell division stops.
AGING

Embryonic stem cells express telomerase,

which allows them to divide repeatedly and
form the individual. In adults, telomerase is
highly expressed only in cells that need to
divide regularly, especially in male sperm
cells but also in epidermal cells, in activated T
cell and B cell lymphocytes, as well as in
certain adult stem cells, but in the great
majority of cases somatic cells do not express
telomerase.
A comparative biology study of mammalian
telomeres indicated that telomere length of
some mammalian species correlates
inversely, rather than directly, with lifespan,
and concluded that the contribution of
telomere length to lifespan is
unresolved. Telomere shortening does not
occur with age in some postmitotic tissues,
such as in the rat brain. In humans, skeletal
muscle telomere lengths remain stable from
ages 23 –74.
 
In baboon skeletal muscle, which consists of
fully differentiated post-mitotic cells, less than
3% of myonuclei contain damaged telomeres
and this percentage does not increase with
age. Thus, telomere shortening does not
appear to be a major factor in the aging of the
differentiated cells of brain or skeletal muscle.
In human
liver, cholangiocytes and hepatocytes show
no age-related telomere shortening. Another
study found little evidence that, in humans,
telomere length is a significant biomarker of
normal aging with respect to important
cognitive and physical abilities.
Some experiments have raised questions on
whether telomerase can be used as an anti-
aging therapy, namely, the fact that mice with
elevated levels of telomerase have higher
cancer incidence and hence do not live
longer. 
CANCER STEM CELLS 
They are cancer cells which are found
within tumors or hematological cancers that
possess characteristics associated with
normal stem cells, specifically the ability to
give rise to all cell types found in a particular
cancer sample. Cancer stem cells are
therefore tumorigenic, perhaps in contrast to
other non-tumorigenic cancer cells. Cancer
stem cells may generate tumors through the
stem cell processes of self-renewal and
differentiation into multiple cell types. Such
cells are hypothesized to persist in tumors as
a distinct population and cause relapse
and metastasis by giving rise to new tumors.
Therefore, development of specific therapies
targeted at Cancer stem cells holds hope for
improvement of survival and quality of life of
cancer patients, especially for patients
with metastatic disease.Existing cancer
treatments have mostly been developed
based on animal models, where therapies
able to promote tumor shrinkage were
deemed effective.
CONCLUSION

In recent years, many isolation and culture

technologies have been proposed. These
technologies have promoted the application of
the stem cells on research of disease
mechanism and clinical therapy. However,
most types of stem cells have their own
disadvantages for therapeutic applications,
such as lack of availability, risk of immune
rejection, directional regulation, and ethical
controversy.
To monitor the efficiency of stem cell therapy
and develop new isolation and culture
technology, it is necessary to improve
molecular imaging techniques. Although none
of these imaging technologies fulfill all of the
requirements needed for stem cell therapy
research at present, their improvement and
the development of multimodality molecular
imaging system will promote more effectively
the understanding of stem cell therapy biology
and its mechanisms.

BIBLIOGRAPHY