Journal of Experimental Therapeutics and Oncology, Vol. 8, pp. 223–233
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Role of stem cell research in therapeutic purpose – a hope for new
horizon in medical biotechnology
Ajit Kumar Saxena*, Divya Singh and Jyoti Gupta
Center of Experiential Medicine and Surgery, Faculty of Medicine, Institute of Medical Sciences, Banaras Hindu
University, Varanasi-221005, INDIA
*Correspondance to: Dr. Ajit K Saxena, Center of Experiential Medicine and Surgery, Faculty of Medicine, Institute of Medical
Sciences, Banaras Hindu University, Varanasi-221005, INDIA. Telephone: 0542-2307549, 0542 670 2196; Fax: 0542-2367568.
E-mail: [email protected]
(Received December 02, 2009; revised February 22, 2009; accepted February 22, 2009)
While the WHO’s general alignment for malignancies
& diabetic impacts only one quarter of the world’s
population, the Indian population is negatively skewed
outside of such malignancies & diabetic range. Stem
cells (SCs) are undifferentiated highly specialized kinds
of cell types having capacity to renew itself, found in
different tissue or organ. SCs are capable of dividing
for long period of time to furnish grow different cell
types with specific functions. It took about twenty years
to gain knowledge of how to grow embryonic stem cell
in-vitro. The primary roles of adult stem cells in a living
organism are to renew or maintain and repair the injured
tissue in which they are found. SCs are classified in to
two categories on the basis of their origin and their
functional properties. First the embryonic stem cells
originate from the inner cell mass of the blastocyst,
while second is of adult stem cells. Another category of
stem cells are the amniotic fluid derived embryonic cells
(AFEc) having equally important cells which transform
into various types of tissues present in fat, bone,
muscles, liver and blood vessels. The main advantage
of AFEc is to use these cells without or disturbing or
touching embryo. Embryonic stem cell expresses
specific markers of self renewal and pluripotency
including transcription factor like SOX-2, LIF etc.
Bone - marrow contains two kinds of stem cells, one
haemotopoietic which form the blood and second stroma
which form mixed cell population like bone, cartilage fat
and fibrous connective tissue. Cellular differentiation of
stem cells is inimitable and based on either intrinsic
or extrinsic signals and during migration cancer stem
cell loses cell polarity which leads to epithelial to
mesenchymal transition (ENT). These signals named
genes which carry coded instructions (novel molecules)
for all the structure and function. External signals are
chemical molecules secreted by other neighboring
cell through physical contact (paracrine regulation).
Efforts are being done to grow both embryonic and adult
stem cells using “tissue culture engineering” in vitro.
SCs could be used for various therapeutic purposes
like Parkinson’s patients , Alzheimer’s disease & other
neurological disorders patients, repairing for damaged
heart muscles and for type I diabetes patients as an
alternative source of chemotherapy including trauma
patients which is not only expensive but lack of side
effect too.
Key words: Adult stem cells, Tumors stem cells,
Embryonic stem cell, Bone- marrow
1. Introduction
Stem cell (SC) is one of the most fascinating
area of modern biology today, because of expanding fields of scientific inquisition and research. SC
raises several questions as rapidly as it generates
new discoveries. Research on stem cells contributes advance knowledge of modern medicine which
explores the impetus how a new organism developed
from a single cell and healthy cells replace damaged cells in adult organisms. SC research on cancer begun in 1960s where normal processes derail.
In 2003, Richard John, characterized a cancer stem
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Saxena et al.
cell population from multiple myloma. The fastest
growing stem cell has been isolated from medulloblastoma. The cancer cells perceive the same potential
to proliferate and expand the diseases but in most of
the cancer cells have limitation. The tumor generating
cell share an important traits with stem cells including unlimited life span and have capacity to generate
different type of other cell, hence, considered to be
cancer stem cell. This promising area of technology
is motivating to biomedical scientists to investigate
the possibility of cell-based therapies to treat drastic
diseases.
1.Cancer treatment must target stem cells to
eradicate the diseases.
2.Several pathways are known to malignancies but seem to become apparent because we
believe cancer arises due to accumulation of
oncogeneic changes within the key genes leads
to abnormal growth and transformation to
cancer cells.
India is a vast country having more than one billion
population. According to WHO reports, year 2030 will
have 366 million people suffering from diabetes alone
which will roughly contributes to 1/4th world diabetic
population. By the year 2010, India will have more cardiac patients than any other country in the world. The
number of patients awaiting transplantation is continuously increasing, and a shortage of available deceased
organ donors is the major limitation for organ allotransplantation (1). With support from various governmental
organization and policy makers- it is hoped that India
will move ahead to realized the full potential of stem
cell. Stem cell research is a difficult scientific and
moral issue. It offer great promise for curing disease
injuries, but also poses the thereat of turning sacred
human components into factory farm parts. In 1998
scientists discovered how to isolate stem cells in the
laboratory from human embryos in test tubes solely to
experiment on them.
Stem cells can give rise to specialized cells the process called differentiation. Scientists are just commencement to understand the signals inside and outside cells
that trigger stem cell differentiation. The internal signals are controlled by a cell’s genes, which are interspersed across long strands of DNA, and carry coded
instructions for all the structure and functions of a cell.
The external signals for cell differentiation include
chemicals secreted by other cells, physical contact with
neighboring cells, and certain molecules in the microenvironment (2).
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Table 1. In brief some degenerative disease that can
be treated with cellular transplantation
Disorders
Cells required for
transplantation
Alzheimer’s disease
Diabetes
Cardiovascular disease
Liver disease
Multiple sclerosis
Osteoarthritis
Spinal cord injuries
Nerve cell
Islet cells
Cardiomyocytes
Hepatocytes
Glial cells
Crondriocytes
Nerve cells
2. Origin
Adult stem cells are growing in most of the laboratories to find ways to how to grow in culture and manipulate them to generate specific cell types so that they can
be used to treat during injury or disease. The potential
treatment include replacing the dopamine producing
cells in the brains for Parkinson’s patient, developing
insulin- producing cells for type - 1 diabetes and repairing damaged heart muscle following a heart attack with
cardiac -muscle cells as documented in Table-1.
3. Characteristic feature
Stem cells serving as a variety of repair system for the
body, they can theoretically divide without limit to replenish other cells. When a stem cell divides, each new cell
has the potential to either remain a stem cell or become
another type of cell such as a muscle cell, a red blood cell,
or a brain cell (3). Research on stem cells is progressing
knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in
adult organism. Cell-based methods whereby stem cells
are induced to differentiate into the specific cell types
required to repair damaged or depleted adult cell populations or tissues (4). The important features are1. Cells are capable of dividing and renewing themselves for long period of time,
2. Cells are unspecialized, and
3. Cells can give rise to specialized cell types with
specific functions.
Cancer stem cells has the ability to self regeneration by dividing without differentiating and give rise to
unlimited abnormal differentiated cells which make up
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Role of stem cells in medicine
the bulk of tumor. The existence of the cancer stem cells
that derived from tumor has been documented in several blood cancer and different type of solid tumors.
4. Type of stem cells
Efforts are being done to establish 200 human
embryonic stem cells lines across the world, only 78
cell lines have been registered with National Institute
of Health and 22 cell lines of these are available for
clinical research. All the stem cell lines were grown
on mouse embryonic feeder (MEF) layers and thus not
suitable for clinical use (5)
In India after obtaining institute ethics committee
permission and written informed consent from the couples attending IVF clinics embryonic stem cell lines are
establish into various lineages with well establish techniques (6). Stem cell therapy is part of a new alternative medicine called “regenerative medicine” which is
emerging as a multidisciplinary field involving molecular & cell biologists, embryologists, pathologists and
clinicians. It holds a lot of promise to cure various age
related degenerative diseases•
•
Embryonic stem cells, and
Adult stem cells.
I. Embryonic stem cells (ESCs) – Specifically embryonic stem cells are derived from embryos that develop
from eggs that have been fertilized in- vitro clinic and
then donated for research purposes with informed consent of the donors. Primitive or undifferentiated cells
obtained from the embryo that have the potential to
become a wide variety of specialized cell types. ESCs
lines have been cultured under in-vitro conditions which
allow proliferating without differentiation for months to
years (7).
They are not derived as typically four or five days
old and are a hollow microscopic ball of cells called the
blastocyst (8). It includes three structures; the trophoblast, is the layer of cells that surrounds the blastocyst;
the blastocoel, is the hollow cavity inside the blastocyst
and the inner cell mass, which is a group of approximately 30 cells at one end of the blastocoel (9). Once cell
lines are established, or even before that stage, batches
of them can be frozen and shipped to other laboratories
for further culture and experimental studies (10).
How to characterize embryonic stem cells
During the process of proliferation and differentiation of embryonic stem cell lines at various stages
exhibit the fundamental properties that make them
embryonic stem cells. This process is called characterization (11).
The standard protocol to tests human embryonic
stem cells still have not been approved by the scientists
due to ethical reasons. Although, the most of the labs
that grow human embryonic stem cell lines use several
kinds of tests to show important biological properties
and functions for experimental studies (12, 13). These
tests includes: •
•
•
•
Stem cells can be grow for many months using sub
culturing because of their capability of long-term
self renewal. Cells seem to be healthy and remain
undifferentiated as inspected routinely under
microscope.
Using specific techniques to determine the presence
of surface markers are found only in undifferentiated cells of a protein called Oct-4 (transcription
factor) which helps to turn genes on and off.
Examining the chromosomes morphology to assess
whether the chromosomes are damaged or changed
in number.
Determining whether the cells can be subcultured
after freezing and thawing.
The characterization of pluripotency in human
embryonic stem cells are -1) the cells are allowing to
differentiate spontaneously in-vitro; 2) manipulating the
cells that differentiate to form specific cell types; or 3)
injecting the cells into an immunosuppressed mouse to
test the development of a benign tumor (14). Stem cells
are important for living organism for numerous reasons.
In the 3 to 5 day old embryo, called a blastocyst, a small
group of about 30 cells called the inner cell mass gives
rise to the hundreds of highly specialized cells needed
to make up adult organism (15). Embryonic stem cells
derived from the blastocytes are capable of self renewal
and can be remain in an undifferentiated state in-vitro
for indefinite lineages (16). Stem cell research involves
transferring nuclei of somatic cells into enucleated
oocytes with the aim to derive embryonic stem cells
with the same genetic makeup as the ‘donor’ cell. From
a clinical perspective when transplanted, should not be
rejected due to incompatible immune response (17).
HUMAN STEM CELLS IN
AMNIOTIC FLUID
As powerful as embryonic stem cells and protect
babies in the womb, may be “pluripotent” in nature
to give rise any type of tissue in the body – muscle,
bone, blood, nerve and liver cells’. ‘Stem cells will
provide a valuable resource for tissue repair and
for engineered organs as well.
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The amniotic fluid- derived stem (AFSc) cells to
transform into many different types of tissue found
in fat, blood vessels, liver, muscles and bone as well
as central nervous system. This variety comprises all
three embryonic germ layers: the mesoderm the progenitor of bone, muscle and connective tissue; endoderm,
which develop into digestive organ as well as lung; and
ectoderm which became nerve, skin and brain (18). The
main advantage of AFS cell is the embryo should not be
injured during harvesting. AFSc lie between embryonic
and adult stem cells in that the former expand quickly,
and can develop into tumors whereas the latter will not
become cancerous, but grow very slowly.
Embryonic stem cell express specific markers as
documented in Table-2 required for self renewal and
pluripotency including transcription factor Oct-4,
Nanog, Sox-2, STAT-3 stage specific embryonic antigen (SSEA) and alkaline phosphatase (AP). This also
exhibit high telomerase activity responsible for cell
proliferation. Leukemia inhibitory factor (LIF) has
also been used extensively to explore the mechanism
for pluripotency and cell differentiation (19). During
cultures pluripotent cells also looses the activity of
transcription factor (Oct-4) after depletion of LIF. The
detailed understanding of the molecular mechanism
which control cellular differentiation as unique property
is still not known (20). The specific factors and condition that allow stem cells to remain unspecialized are
quite a lot of interest to the scientists. Since many years
of trial and error to learn to grow stem cells in the laboratory without spontaneous differentiation into specific
cell types (21) took about 20 years to learn how to grow
human embryonic stem cells in the laboratory following the development of culture conditions. Therefore,
stem cell is an important area of research to understand
the signals in a mature organism that cause a stem cell
population which proliferate and remain unspecialized
until the cells are needed for repair of a specific tissue. Such information is significant for researchers to
grow large numbers of unspecialized stem cells in the
laboratory.
Embryonic stem cells have also been originated
from nuclear transfer (NT) and parthenogenetic
embryos in few species (22, 23). Major application
of these cell lines includes the targeted mutation of
specific genes by homologous recombination discovery of new genes by gene trap strategies and production of clones. Efforts are being continued for AFS
cells using mouse model to differentiate in to the tisTable 2. List of the common pluripotent marker for ES
cells
S. No
1
Markers
ESC
Nanog
+
2
Sox 2
+
3
SSEA-1
+
4
Alkaline Phosphatase
+
5
STAT-3
+
Figure 1. Human embryonic stem cells differentiating into different organs.
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Role of stem cells in medicine
sue found in heart, pancreas, kidneys and testis due to
pluripotent nature (24). Somatic cell nuclear transfer
is another useful technique for the study of drug toxicology in embryonic cell lines derived from a somatic
cell lines carrying a certain disease(s) as mentioned
in table-1.
II. Adult Stem Cells (ASCs) – The history of research
since 40 years ago on adult stem cells began and generated a great deal of excitement for the scientists. ASCs
are undifferentiated cells found in different tissues that
can renew themselves and (with certain limitations) differentiated to yield all the specialized cell types from
which it originated (25). ASCs are found in many more
tissues used for transplants. In fact, adult blood forming
stem cells from bone - marrow have been used in transplantations over the last 30 years (26). Certain kinds
of ASCs seem to have the ability to differentiate into
a number of different cell types in- vitro which can be
used in therapies for many serious common diseases
(Table-1).
In 1960s researchers discovered that the bonemarrow contains two kinds of SCs population- first
hematopoietic stem cells which form all the types of
blood cells in the body while second population called
bone- marrow stroma was discovered a few years later.
Stromal cells are a mixed cell population that gener-
ates bone, cartilage, fat and fibrous connective tissue as
mentioned in figure-2 (27).
Adult stem cells typically generate the cell types
of the tissues in which they reside (niche). A bloodforming adult stem cell in the bone- marrow normally
gives rise to the many types of blood cells including red
blood cells, white blood cells and platelets as shown
in figure-2. Recently, it had been thought that a bloodforming cell in the bone-marrow failed to give rise to
the cells of a very different tissue, such as nerve cells
of the brain (28).
However, a number of experiments over the last
several years have raised the possibility that stem
cells from one tissue may be able to give rise to cell
types of a completely different tissue, a phenomenon known as plasticity. Examples of such plasticity
include blood cells turn into neurons and heart muscle
while liver cells that can be made to produce insulin (29). Simultaneously, scientists are also exploring
the possibility of using adult stem cells for cell-based
therapies as an alternative tool in medical biotechnology (30).
Similarly, in 1960s scientists also discovered two
regions of the rats’ brain that contained dividing cells
which later become nerve cells. They agreed that the
adult brain does contain stem cells which are able to
generate three major cell types- astrocytes and oligodendrocytes, which are non-neuronal cells and neuronal
Figure 2. Stem cells forming hematopoietic system from bone marrow.
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cells. The fastest growing stem cells are in human brain
cancer (medulloblastoma).
STEM CELL MAY END INSULIN NEED
Because SCs have been found to mature into
beta cells once they receive a stimulus identified
as GLP1 from the body. A protein inside the cells
called PDX1 then start producing insulin.
In contrast, stem cells have been reported from
many tissues (heart, kidney, muscle, brain, milk teeth
etc.) which differentiate slowly (31). Hematopoietic
and mesenchymal stem cells are found in the bone marrow, cord blood as well as peripheral blood. These cells
play an important role to bring about homeostasis in
our body. They continuously generate new progenitors
and mature functional cells to replace old cells. The
other tissues like skin, gut mucosa, muscle, cartilage,
nerves, cornea, retina, liver, endometrium etc. regulated
by stem cells. Postnatal adult stem cells are considered
as a promising tool for regenerative therapy because of
the property of transdifferentiation (32).
Stem cells are important for living organisms because of many reasons. In the 3-to 5-day-old embryo,
stem cells give rise to the multiple specialized cell types
that make the heart, lung, skin and other tissues require
during injury or disease (33).
Efforts are being made to understand the fundamental properties of stem cells that associated with
long- term self renewal:a. Embryonic stem cells (ESCs) proliferate for long
periods of time in the laboratory without differentiating while adult stem cells cannot, and
b. Factor(s) in living organisms that normally regulate SC proliferation for self-renewal.
Identification of adult stem cells
Generally scientists do not reach in to conclusion
how to identify adult stem cells, however they often use
one or more of the following three methods:1. Labeling the cells in a living tissue with molecular markers which determine the specialized cell
types,
2. Removing the labeled cells in culture from animal and then transplant them back into another to
determine whether the cells repopulate; and
3. Isolated cells grow in-vitro and manipulate by adding growth factors or introducing new genes.
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5. How to maintain stem cells in
laboratory
Growing cells in the laboratory is known as cell culture technology, involves isolating human embryonic stem cells by transferring the inner cell mass into a
plastic culture dish that contains a nutrient broth known
as culture medium. The cells divide and spread over
the surface of the culture dish is typically coated with
embryonic stem cells that have been treated to inhibit
the division (34). This coating layer of cells is called
a feeder layer. The reason for having the treated cells
in the bottom of the culture dish is to give the inner
cell mass and cell can be attached to a sticky surface.
The feeder cells also release nutrients into the culture
medium either by autocrine or paracrine regulation.
The best results are achieved by dedicating appropriate space, equipment and person to the project. ESC
project is expensive, time consuming but in long term
help to cut down time and money which require more
care and attention than other cells cultured in the laboratory. Recently, a significant scientific achievement
have been developed by growing embryonic stem cells
without the feeder cells to avoid the risk factor from
viruses or other macromolecules which may transmit
to the human cells (35).
i. Culture conditions: ESCs require special attention
on a daily basis, which is best provided by dedicated
personal that are able to monitor day-to-day changes
in the cultures. The skills are required to determine
how to passage the cells, initiation of experiments,
freeze stock, terminate the culture or cryopreservation and start over. Few cell lines can be transformed
from conventional culture condition to grow on gelatin without feeder layer or in minimal media. These
cell lines are grown on high quality medium that contains fetal bovine serum (FBS) with leukemia inhibitory factor (LIF). This is most common and successful
culture method till to date (36).
ii. Incubator: The ESC cultures are sensitive or limited
to access in and out of the incubator. The cells are
sensitive to changes in pH. It is important to know
the pH of the basal medium are regulated by the concentration of CO2 and most of the labs use 5% CO2
to culture. Although, bicarbonate levels in DMEM
work optimally to maintain mammalian physiological pH in a 10% CO2 environment.
iii. Culture medium: Today, there is large number of
high quality and reliable sources of basal media and
supplements are available for successful and conventional experiments. However, there is a certain
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Role of stem cells in medicine
amount of variability in culture media, which comes
primarily from the addition of serum, or serum substitutes in different concentration of animal origin.
Serum is a sensitive culture supplement and performance of cell culture depends on the number of
factors like the age, diet and country of origin of
animal. Many researchers use different combination
of serum substitutes or addition of growth factors
to improve the efficiency of ESC cultures during
experimentation. It is important to remember that
currently available serum substitutes are biological
materials derived from serum (37).
iv. Monitoring and analysis: The morphology of ESC
culture is dependent on the substrate. Mouse ESC
grows rapidly and dividing very fast, within 10 to
20 hours reaches in either doubling in number or
in confluency, depending on the nature of cell lines
(germ line chimeras). The cells have a large nuclear
to cytoplasmic ratio grow in small, tightly clustered
colonies with tight phase bright borders, although it
is difficult to identify individual cells within a colony
of undifferentiated ESC (38).
v. Karyotyping Analysis: Chromosomal analysis is an
important aspect for characterization of gene mutation if cells are allowed to grow for longer period of
time. Monitoring of chromosomes in the ESC line is
essential because of the different culture conditions,
concentration of serum and allow to grow for longer
period of time (i.e. more than 6 month or longer).
Therefore it is recommended to prepare a karyotype
every 1015 passages, although it is very difficult to
find out a normal karyotype. Despite all the new
markers of pluripotency are well-known but the best
test for pluripotency is the development of germ line
chimeras after ESCs are injected into a blastocyst to
determine how efficiently they grow.
vitro and in- vivo. These unique features lead to develop
excitements and interest to the scientists (39).
7. Cord blood banking
The cord blood is a rich source of both hematopoietic
and mesenchymal stem cells. It has a potential for both
hematopoietic transplantation and regenerative medicine (40). Earlier it was thrown away because of lack
of knowledge. The cord blood has a lower risk of viral
infection and severity of acute & chronic graft versus
host disease (41). Owing to the limited amount of blood
collected, cord blood has usually been used in children
and small adults, whose weight is generally exist less
than 40 kg (42, 43). More recently, however, the use of
cord blood has been extended to include adults.
8. Embryonic Stem Cell line
The quality of the ESC line at the time of initiating the experiment is one of the most important factors
to determine the success of an experiment, whether the
experiment is in-vitro differentiation or in-vivo production of chimeric mice. In general, the passage number
has the biggest overall impact on the pluripotency of
ESC lines (44). A fully defined culture media is required
to promote cell proliferation or to improve differentiation of cells as measure to test the pluripotency. This
will act as a boon to the medical science to improve
the potential of therapeutic applications (45). Although,
in many laboratories are developing culture media for
specific cell types who are in an undifferentiated state
during routine cell culture.
9. Significant work has to be done
6. Mesenchymal stem cells (MSCs)
Mesenchymal stem cells (MSCs) are multipotent
adult stem cells able to differentiate into a variety of
cell types such as osteoblasts, chondrocytes, myocytes,
adipocytes, and beta-pancreatic islets cells through
involvement of 84 genes expression to maintain pluripotency and self-renewal status. MSCs can be isolated
from several tissues like bone marrow, placenta etc.
These adult stem cells offer many advantages for therapeutics purpose like ease of isolation, in-vitro expansion potential i.e. expanded in culture up to more than
50 passages with stable phenotype. MSCs have also
been shown to possess immunosuppressive activity in-
Human ES cell-based transplantation therapy holds
great promise to successfully treat a variety of diseases
(e.g., Parkinson’s disease, diabetes and heart failure)
because stem cells have dual ability to proliferate and
differentiate indefinitely into various types of tissues.
For successful clinical trials many barriers are still
remains. ES cells form an ideal tool to study the process of early embryogenesis in- vitro due to its ability
to recapitulate embryonic differentiation. ESCs could
potentially provide an unrestricted supply of tissues for
human transplantation. These cells have a major potential as in-vitro model for drug screening and toxicity
evaluation program as follows:-
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1. To provide long term therapeutically benefits upon
grafting into damaged tissues;
2. Growth and genetic manipulation of human ES
cells; and
3. To differentiation into specific cell types.
However, there is still a need to characterized novel
factor (s) which allows serum-free and feeder-free
expansion of ES cells. Simultaneously, there is also
require an appropriate primate model for clinical trials based on ES cells regenerative potential but perquisite for ethical clearance is required to conduct such
studies.
Several disease models have been demonstrated
using hES cells for therapeutic agents such as myocardial infections, diabetes mellitus and Parkinson’s disease. Prior to clinical trials in humans, two issues are
still unexplained:i. Risk to the development of teratocarcinomas in the
recipient, and
ii. Immunological rejection by recipient.
10. Why stem cells are important for
therapeutic purposes?
Stem cells have two important characteristics features which distinguish them from other cell types.
First- they are unspecialized cells, renew themselves
for longer periods of time and second are under physiological or experimental condition they can be induced
to become cells of the organ such as pancreas (46).
With the advancement of in- vitro technology, scientists want to grow stem cells in the laboratory to learn
more about their essential features which makes them
different from specialized cell types. Now, it becomes
possible for the scientists to use these cells not only
for therapeutic purpose, but also for screening new
drugs and toxins to understand the genesis of “birth
defects” (47). Since 1998, human embryonic stem
cells have been studying intensively to know the fundamental properties including determining how stem
cell remains unspecialized or self renewing capacity
for many years. The study has been further extended to
identify the factors or signals which make the stem cell
as highly specialized cells.
Scientists have developed a number of new strategies for human stem cell therapy, to produce dopamine
in neurons from stem cells in -vitro model before transplantation into human with Parkinson’s disease. The
successful cultures of an unlimited supply of dopamine
neurons could make neurotransplantation widely available for Parkinson’s patient.
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“Stem cells can be helpful for screening drugs
and prevent “birth defects” by tissue engineering
because of high therapeutic values could be used
for traumatic spinal cord injury, Parkinson’s disease and heart disease”
In the developing fetus stem cells give rise to the multiple specialized cell types which develop the heart, lung,
skin and other tissues. In some adult tissues, such as bone
marrow, muscle and brain distinct populations of adult
stem cells generate replacement for cells which are lost
through normal process or injury or disease (48). One of
the fundamental properties of stem cell is which it does
not have any tissue-specific structure that allows it to perform specialized functions including it cannot pump blood
through the body (heart muscle cell); cannot carry oxygen molecules into bloodstream (RBC); and it cannot fire
electrochemical signals (nerve cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle, blood cells, or nerve cells because these
cells are capable of dividing and renewing themselves for
long periods. Unlike muscle cells, blood cells, or nerve
cells-which do not normally replicate themselves. Initial
population of stem cells that proliferates for many months
in the laboratory can yield millions of cells.
Now scientists are just begun to understand the signals
are controlled by a cell’s genes which are interspersed
across long strands of DNA and carry coded instruction
for structure & functions of a cell. Several genes and the
cascades of events triggered by their activity known as
genetic pathway, play key roles in dictating stem cells
fate and function. Among these signaling pathways
headed by Bmi-1, Notch, and Wnt genes are involved in
the development of malignancies. The external signals
required for cell differentiation are chemicals secretion
or physical contact with neighboring cells (autocrine or
paracrine regulation). Therefore, many questions about
stem cell differentiation are still unanswered, such as
nature of internal and external signals for cell differentiation are remain same or specific sets of signals can
be identified to promote differentiation into specific
cell types? To answer of these questions scientists are
engaged to find out new ways of regulating stem cell differentiation in-vitro. These cells could be further used
for specific purposes including cell-based therapies.
11. Distinguish features between
embryonic and adult stem cells
Human embryonic and adult stem cells have both
advantages and disadvantages regarding potential use
of regenerative therapies. In fact, adult and embryonic
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Role of stem cells in medicine
stem cells differ quantitatively during differentiation.
Embryonic stem cells can become all cells types of
the body due to pluripotent in nature. ASCs are generally limited to differentiating into different cell types
of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist because of
increasing the number of cell types. Large numbers of
embryonic stem cells can be relatively easily grown in
laboratory, while adult stem cells are difficult although
efforts are being made to improve these cell culture
technologies. Large numbers of cells are required for
stem cell therapies because of critical differences in
between the two (49).
12. Relevant questions concern to
stem cells
What are the sources of adult stem cells in the body?
Are they “arises” from embryonic stem cells, or some
other way?
•
•
•
•
•
Why do they remain in an undifferentiated state
in the organ while all the cells around them have
differentiated?
How many kinds of adult stem cells exits and in
which tissue?
Do adult stem cells normally exhibit plasticity, or manipulate them experimentally before
transplantation?
What are the signal(s) or factor(s) required to regulate the proliferation and differentiation of stem
cells at the site tissue damage or injury?
Does a single type of stem cell exist in the bone
marrow?
13. Challenges for Stem Cell
Research
for therapeutic purpose. Today, the available supplies
of stem cells are either from donated organs or tissue
needed for transplantable to replace ailing or destroyed
tissue. Stem cells offer the possibility of a renewable
source of replacement cells, tissue to treat disease
including Parkinson’s and Alzheimer’s disease, spinal
cord injury, stroke, burns, heart disease, osteoarthritis,
rheumatoid arthritis and in people who suffer from type
I diabetes. Because the cells of the pancreas that normally produce insulin are destroyed by the patient’s own
immune system or unknown reason. Recent studies indicates that it may be possible to direct the differentiation
of human embryonic stem cells in cell-culture to form
insulin producing cells which eventually could be used
in transplantation therapy for diabetics patients (50).
The following steps will be required to learn precisely and successful stem cell transplantation in the
laboratory for cell based treatment in the above mentioned disorders:•
•
•
•
•
•
Survive in the recipient after transplant.
Extensive proliferation to generate sufficient amount
of tissue.
Differentiate into desired cell- type (s).
Integrate into the surrounding tissue after transplant.
Function suitably through out the recipient’s life.
Avoid side effects to the recipient.
14. Conclusion
This review is presented on the possible role of stem
cell research including characterization; different types,
maintenance and applied physiological role, try to covers different discipline including cancer for therapeutics in biomedical sciences.
Acknowledgement
In medicine, human stem cells act as boon and
could be used as an alternative tool for therapeutic
program because of pluripotent nature of cells. Cancer cell lines are used to screen for anti-tumor drugs
because of similarity in growth kinetic to pluripotent
stem cells. However, to screen drugs effectively, the
conditions must be identical when comparing different drugs. Therefore, scientist will have to be able precisely control the differentiation of stem cells into the
specific cell type on which drugs will be experienced.
Existing knowledge of the signals controlling cell differentiation for drug testing is still lacking.
The important application of human stem cells is the
generation of new cells and tissues that could be used
The author AKS is thankfully acknowledge to
the Director, Institute of Medical Sciences, BHU for
continuous and consistently encouragement during the
preparation of manuscript.
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