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ISSN 0975-6299
Vol 3/Issue 1/Jan – Mar 2012
International Journal of Pharma and Bio Sciences
PHARMACOLOGY
REVIEW ARTICLE
STEM CELL THERAPY-AN OVERVIEW
SREELATHA MACHERLA* AND NAGARAJ KUMAR MURAHARI
Siddhartha Institute of Pharmaceutical Sciences, Jonnalagadda, Narasaraopet-522601, Guntur District,
Andhra Pradesh, India
SREELATHA MACHERLA
Siddhartha Institute of Pharmaceutical Sciences, Jonnalagadda, Narasaraopet-522601,
Guntur district, Andhra Pradesh, India
ABSTRACT
Stem cells are biological cells found in all multicellular organisms, that can divide through
mitosis and differentiate into diverse specialized cell types and can self renew to produce more
stem cells. In mammals, there are two broad types of stem cells: embryonic stem cells that are
isolated from the inner cell mass of blastocysts, and adult stem cells that are found in various
tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body,
replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the
specialized cells, but also maintain the normal turnover of regenerative organs, such as blood,
skin, or intestinal tissues. Medical researchers believe that stem cell therapy has the potential
to dramatically change the treatment of human disease. A number of adult stem cell therapies
already exist, particularly bone marrow transplants that are used to treat leukemia. In the
future, medical researchers anticipate being able to use technologies derived from stem cell
research to treat a wide variety of diseases including cancer, Parkinson's disease, spinal cord
injuries, Amyotrophic lateral sclerosis, multiple sclerosis, and muscle damage, amongst a
number of other impairments and conditions.
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KEYWORDS
Stem cell, Adult & Embryonic stem cells, Tissue Regeneration, Stem cultures,
INTRODUCTION
Stem cells are biological cells found in all
multicellular organisms, that can divide through
mitosis and differentiate into diverse specialized
cell types and can self renew to produce more
stem cells. In mammals, there are two broad
types of stem cells: embryonic stem cells that are
isolated from the inner cell mass of blastocysts,
and adult stem cells that are found in various
tissues. In adult organisms, stem cells and
progenitor cells act as repair system for the
body, replenishing adult tissues. In a developing
embryo, stem cells can differentiate into all the
specialized cells, but also maintain the normal
turnover of regenerative organs, such as blood,
skin, or intestinal tissues.
IMPORTANCE OF STEM CELLS:
Stem cells have the remarkable potential to
develop into many different cell types in the body
during early life and growth. In addition, in many
tissues they serve as a sort of internal repair
system, dividing essentially without limit to
replenish other cells as long as the person or
animal is still alive. When a stem cell divides,
each new cell has the potential either to remain a
stem cell or become another type of cell with a
more specialized function, such as a muscle cell,
a red blood cell, or a brain cell.
Stem cells are distinguished from other cell types
by two important characteristics. First, they are
unspecialized cells capable of renewing
themselves through cell division, sometimes after
long periods of inactivity. Second, under certain
physiologic or experimental conditions, they can
be induced to become tissue- or organ-specific
cells with special functions. In some organs,
such as the gut and bone marrow, stem cells
regularly divide to repair and replace worn out or
damaged tissues. In other organs, however,
such as the pancreas and the heart, stem cells
only divide under special conditions.
SOURCE FOR STEM CELLS:
Stem cells are a class of undifferentiated cells
that are able to differentiate into specialized cell
types. Commonly, stem cells come from two
main sources:
1. Embryos formed during the blastocyst phase
of
embryological
development
(embryonic stem cells) and
2. Adult tissue (adult stem cells).
Both types are generally characterized by their
potency, or potential to differentiate into different
cell types (such as skin, muscle, bone, etc.).
ADULT STEM CELLS
Adult or somatic stem cells exist throughout the
body after embryonic development and are found
inside of different types of tissue. These stem
cells have been found in tissues such as the
brain, bone marrow, blood, blood vessels,
skeletal muscles, skin, and the liver. They remain
in a quiescent or non-dividing state for years until
activated by disease or tissue injury.
Adult stem cells can divide or self-renew
indefinitely, enabling them to generate a range of
cell types from the originating organ or even
regenerate the entire original organ. It is
generally thought that adult stem cells are limited
in their ability to differentiate based on their
tissue of origin, but there is some evidence to
suggest that they can differentiate to become
other cell types.
EMBRYONIC STEM CELLS
Embryonic stem cells are derived from a four- or fiveday-old human embryo that is in the blastocyst phase
of development. The embryos are usually extras that
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have been created in IVF (in vitro fertilization) clinics
where several eggs are fertilized in a test tube, but
only one is implanted into a woman. Sexual
reproduction begins when a male's sperm fertilizes a
female's ovum (egg) to form a single cell called a
zygote. The single zygote cell then begins a series of
divisions, forming 2, 4, 8, 16 cells, etc. After four to
six days - before implantation in the uterus - this
mass of cells is called a blastocyst. The blastocyst
consists of an inner cell mass (embryoblast) and an
outer cell mass (trophoblast). The outer cell mass
becomes part of the placenta, and the inner cell mass
is the group of cells that will differentiate to become
all the structures of an adult organism. This latter
mass is the source of embryonic stem cells totipotent cells (cells with total potential to develop
into any cell in the body).
In a normal pregnancy, the blastocyst stage
continues until implantation of the embryo in the
uterus, at which point the embryo is referred to as a
fetus. This usually occurs by the end of the 10th
week of gestation after all major organs of the body
have been created. However, when extracting
embryonic stem cells, the blastocyst stage signals
when to isolate stem cells by placing the "inner cell
mass" of the blastocyst into a culture dish containing
a nutrient-rich broth. Lacking the necessary
stimulation to differentiate, they begin to divide and
replicate while maintaining their ability to become any
cell type in the human body. Eventually, these
undifferentiated cells can be stimulated to create
specialized cells.
COMPARISION BETWEEN EMBRYONIC & ADULT STEM CELLS:
Differences
EMBRYONIC
ADULT
How Obtained
By killing a 5 day old human embryo
From you own body cells
Tissue
compatibility
Different DNA-can be rejected as foreign tissue
These are your own cells and will not be
rejected
Infection
If donor has infection it will be transmitted
You cannot infect yourself
Tumors
These can and do form multicellular tumors
These do not form tumors
Feasibility
-More expensive
-More complicated
Cheaper
Easier to do
Morality
Immoral –it kills a human
Completely ethical
Success
Not one human cure to date and future ones are
questionable
Over 80 human diseases and conditions have
been cured
STEM CELL CULTURES
Figure 1
Human embryonic stem cell colony
Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted,
scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but
usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has
been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.
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STEM CELL LINES
Once stem cells have been allowed to divide and The classical definition of a stem cell requires that it
propagate in a controlled culture, the collection of possess two properties:
healthy, dividing, and undifferentiated cells is called a
• Self-renewal - the ability to go through
stem cell line. These stem cell lines are subsequently
numerous cycles of cell division while
managed and shared among researchers. Once under
maintaining the undifferentiated state.(Fig .2).
control, the stem cells can be stimulated to specialize
• Potency - the capacity to differentiate into
as directed by a researcher - a process known as
specialized cell types. In the strictest sense,
directed differentiation. Embryonic stem cells are able
this requires stem cells to be either totipotent
to differentiate into more cell types than adult stem
or pluripotent - to be able to give rise to any
cells.
mature cell type, although multipotent or
unipotent progenitor cells are sometimes
PROPERTIES
referred
to
as
stem
cells
SELF-RENEWAL
Figure 2
Two mechanisms exist to ensure that the stem cell population is maintained:
1. Obligatory asymmetric replication - a stem cell divides into one father cell that is identical to the original
stem cell, and another daughter cell that is differentiated
2. Stochastic differentiation - when one stem cell develops into two differentiated daughter cells, another
stem cell undergoes mitosis and produces two stem cells identical to the original.
POTENCY
Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are
the most potent since they must become every type of cell in the body. The full classification includes
POTENCY DEFINITIONS:
Figure 3
Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become
any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues
and a placenta.
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Figure 4
Human embryonic stem cells
A: Cell colonies that are not yet differentiated.
B: Nerve cell
differentiation potential
• Multipotent stem
Potency specifies the
(the potential to differentiate into different cell
types) of the stem cell.[4]
• Totipotent (a.k.a omnipotent) stem cells
can differentiate into embryonic and
extraembryonic cell types. Such cells can
construct a complete, viable organism.[4]
These cells are produced from the fusion
of an egg and sperm cell. Cells produced
by the first few divisions of the fertilized
egg are also totipotent.[5]
• Pluripotent
stem
cells
are
the
descendants of totipotent cells and can
differentiate into nearly all cells,[4] i.e. cells
derived from any of the three germ
layers.[6] The ability to differentiate into
almost all cell types. Examples include
embryonic stem cells and cells that are
derived from the mesoderm, endoderm,
and ectoderm germ layers that are formed
in the beginning stages of embryonic stem
cell differentiation
•
•
cells can differentiate
into a number of cells, but only those of a
closely related family of cells.[4] Examples
include hematopoietic (adult) stem cells
that can become red and white blood cells
or platelets.
Oligopotent stem cells can differentiate
into only a few cells, such as lymphoid or
myeloid stem cells.[4]
Unipotent cells can produce only one cell
type, their own,[4] but have the property of
self-renewal which distinguishes them
from non-stem cells (e.g. muscle stem
cells).
•
IDENTIFICATION OF STEM CELLS
The practical definition of a stem cell is the
functional definition - a cell that has the potential
to regenerate tissue over a lifetime. For example,
the defining test for a bone marrow or
hematopoietic stem cell (HSC) is the ability to
transplant one cell and save an individual without
HSCs. In this case, a stem cell must be able to
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produce new blood cells and immune cells over
a long term, demonstrating potency. It should
also be possible to isolate stem cells from the
transplanted individual, which can themselves be
transplanted into another individual without
HSCs, demonstrating that the stem cell was able
to self-renew.
Properties of stem cells can be illustrated in vitro,
using methods such as clonogenic assays, in
which single cells are assessed for their ability to
differentiate and self-renew.[7][8] Stem cells can
also be isolated by their possession of a
distinctive set of cell surface markers. However,
in vitro culture conditions can alter the behavior
of cells, making it unclear whether the cells will
behave in a similar manner in vivo. There is
considerable debate as to whether some
proposed adult cell populations are truly stem.
DISEASES TREATABLE WITH STEM CELLS
Scientists and researchers are interested in stem
cells for several reasons. Although stem cells do
not serve any one function, many have the
capacity to serve any function after they are
instructed to specialize. Every cell in the body,
for example, is derived from first few stem cells
formed in the early stages of embryological
development. Therefore, stem cells extracted
from embryos can be induced to become any
desired cell type. This property makes stem cells
powerful enough to regenerate damaged tissue
under the right conditions. (fig5)
Figure 5
potential uses of Stem cells
Diseases and conditions in which stem cell
treatment is promising or emerging.[9 Bone
marrow transplantation is, as of 2009, the only
established use of stem cells.
Medical researchers believe that stem cell
therapy has the potential to dramatically change
the treatment of human disease. A number of
adult stem cell therapies already exist,
particularly bone marrow transplants that are
used to treat leukemia.[10] In the future, medical
researchers anticipate being able to use
technologies derived from stem cell research to
treat a wider variety of diseases including
cancer, Parkinson's disease, spinal cord injuries,
Amyotrophic lateral sclerosis, multiple sclerosis,
and muscle damage, amongst a number of other
impairments and conditions.[11][12] However, there
still exists a great deal of social and scientific
uncertainty surrounding stem cell research,
which could possibly be overcome through public
debate and future research, and further
education of the public.
One concern of treatment is the risk that
transplanted stem cells could form tumors and
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become cancerous if cell division continues
uncontrollably.[13]
Stem cells are widely studied, for their potential
therapeutic use and for their inherent interest.[14]
Supporters of embryonic stem cell research
argue that such research should be pursued
because the resultant treatments could have
significant medical potential. It has been
proposed that surplus embryos created for in
vitro fertilization could be donated with consent
and used for the research.
ORGAN AND TISSUE REGENERATION
Tissue regeneration is probably the most
important possible application of stem cell
research. Currently, organs must be donated and
transplanted, but the demand for organs far
.
Treatment of Heart Disease:
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
exceeds supply. Stem cells could potentially be
used to grow a particular type of tissue or organ
if directed to differentiate in a certain way. Stem
cells that lie just beneath the skin, for example,
have been used to engineer new skin tissue that
can be grafted on to burn victims.
BRAIN DISEASE TREATMENT
Additionally, replacement cells and tissues may
be used to treat brain disease such as
Parkinson's and Alzheimer's by replenishing
damaged tissue, bringing back the specialized
brain cells that keep unneeded muscles from
moving. Embryonic stem cells have recently
been directed to differentiate into these types of
cells, and so treatments are promising
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 marrowderived 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.
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Figure 6
Strategies to repair heart muscle with adult stem cells
CELL DEFICIENCY THERAPY
Healthy heart cells developed in a laboratory
may one day be transplanted into patients with
heart disease, repopulating the heart with
healthy tissue. Similarly, people with type I
diabetes may receive pancreatic cells to replace
the insulin-producing cells that have been lost or
destroyed by the patient's own immune system.
The only current therapy is a pancreatic
transplant, and it is unlikely to occur due to a
small supply of pancreases available for
transplant.
BLOOD DISEASE TREATMENT
Adult hematopoietic stem cells found in blood
and bone marrow have been used for years to
treat diseases such as leukemia, sickle cell
anemia, and other immunodeficiencies. These
cells are capable of producing all blood cell
types, such as red blood cells that carry oxygen
to white blood cells that fight disease. Difficulties
arise in the extraction of these cells through the
use of invasive bone marrow transplants.
However hematopoietic stem cells have also
been found in the umbilical cord and placenta.
This has led some scientists to call for an
umbilical cord blood bank to make these
powerful cells more easily obtainable and to
decrease the chances of a body's rejecting
therapy.
CONCLUSION
Medical researchers believe that stem cell
therapy has the potential to dramatically change
the treatment of human disease. A number of
adult stem cell therapies already exist,
particularly bone marrow transplants that are
used to treat leukemia.[10] In the future, medical
researchers anticipate being able to use
technologies derived from stem cell research to
treat a wider variety of diseases including
cancer, Parkinson's disease, spinal cord injuries,
Amyotrophic lateral sclerosis, multiple sclerosis,
and muscle damage, amongst a number of other
impairments and conditions.[11][12] However, there
still exists a great deal of social and scientific
uncertainty surrounding stem cell research,
which could possibly be overcome through public
debate and future research, and further
education of the public.
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