connective tissues. There are many potential
sources for stem cells. Embryonic stem cells
(ESC) are derived from the inner cell mass of a
blastocyst (a very early embryo). Embryonic
germ cells (EGC) are collected from fetal tissue
at a somewhat later stage of development (from a
region called the gonadal ridge), and the cell
types that they can develop into may be slightly
limited. See the electron micrograph of stem cell.
The Stem Cell Research and Applications
Dr.R.V.S.N.Sarma., M.D., M.Sc (Canada)
The benefits to society gained by the
introduction of new drugs or medical
technologies are really fascinating. The
introductions of antibiotics and vaccines, for
example, have dramatically increased life spans
and improved the health of people all over the
world. The science of stem cell therapies,
potentially as important as these other advances,
has entered a phase of research and development
that could lead to unprecedented cures and
palliative treatments. The current excitement
over potential stem cell therapies emanates from
new
understandings
of
genetics
and
developmental biology. Although there is no
way to predict the outcomes from basic research,
there is enough data and evidence to justify all
the enthusiasm and excitement.
Most cells within an animal or human being are
committed to fulfilling a single function within
the body. In contrast, stem cells are a unique and
important set of cells that are not specialized.
Stem cells retain the ability to become many or
all of the different cell types in the body and
thereby play a critical role in repairing organs
and body tissues throughout life. Although the
term stem cells is often used in reference to these
repair cells within an adult organism, a more
fundamental variety of stem cells is found in the
early stage embryo. Embryonic stem cells have a
greater ability to become different types of body
cells than adult stem cells.
Adult stem cells (ASC) are derived from mature
tissue. Even after complete maturation of an
organism, cells need to be replaced (a good
example is blood, but this is true for muscle and
other connective tissue as well, and may be true
for at least some nervous system cells). Because
these give rise to a limited number of cell types,
they are more accurately referred to as
multipotent stem cells, as discussed above. Stem
cells can also be derived from the placenta and
umbilical cord blood immediately after the
delivery of the placenta. These are called
Umbilical cord stem cells (UCSC). Very recently
scientists have harvested stem cells from the
amniotic fluid - termed the Amniotic fluid stem
cells (AFSC).
Current Status of Human Stem Cell Research
Overview: Stem cell is a term to describe
precursor cells that can give rise to multiple
tissue types. There are important distinctions,
however, regarding how developmentally plastic
these cells are; that is, how many different paths
they can follow and to what portion of a
functioning organism they can contribute.
Totipotent stem cells are cells that can give rise
to a fully functional organism as well as to every
cell type of the body. Thus they can form a
whole new animal or human in its entirety.
Pluripotent stem cells are capable of giving rise
to virtually any tissue type, but not to a fully
functioning organism. Multipotent stem cells are
more differentiated and thus can give rise only to
a limited number of tissues. For example, a
specific type of multipotent stem cell called a
Mesenchymal Stem Cell (MSC) has been shown
to produce bone, muscle, cartilage, fat, and other
Fig: The hierarchy of differentiation and potency
1
Knowledge about stem cell science and potential
applications has been accumulating for more
than 40 years. In the 1960s, it was recognized
that certain mouse cells had the capacity to form
multiple tissue types, and the discovery of bona
fide stem cells from mice occurred in 1971.
Limited types of stem cell therapies are already
in use. The most well-known therapy is the stem
cell transplant (a form of BMT- bone marrow
transplant) for cancer patients. In this therapy,
stem cells that can give rise to blood cells (red
and white cells, and platelets) are given to
patients to restore tissue destroyed by high dose
chemotherapy or radiation therapy. But it has
been only recently that scientists have
understood stem cells well enough to consider
the possibilities of growing them outside the
body for long periods of time. With that advance,
rigorous experiments can be conducted, and the
possibility of manipulating these cells in such a
way that specific tissues can be grown is real. It
is impossible to project when actual treatments
or cures might emerge from such research and
draw any time line for therapeutic applications of
research.
A. Human Embryonic Stem Cells (hESC). The
vast majority of experimental data discussed here
are the results of experiments in mice. ES cells
from the mouse have been intensely investigated
since their discovery 18 years ago. Therefore,
what is said about human ES cells assumes in
part that their fundamental properties will
resemble those of mouse ES cells. There is an
abundance of stem cell lines from mammals
including some from human beings. ES cells are
valuable scientifically because they combine
three properties not found together in other cell
lines. First, they appear to replicate indefinitely
without undergoing senescence (aging and death)
or mutation of the genetic material. They are thus
a large-scale and valuable source of cells.
Second, ES cells appear genetically normal, both
by a series of genetic tests and functionally with
genomes derived entirely from ES cells. In these,
cells are developmentally totipotent; when
inserted into an early embryo, they join the host
cells to create a normal organism, differentiating
into every cell type of the body. ES cells can also
differentiate into many cell types in tissue culture,
including neurons, blood cells and cardiac and
skeletal muscle. The normal embryo has about
100 cells with the properties of ES cells that
exist for about one day and then develop into
more advanced cell types. The isolation and
subsequent growth of ES cells in culture allow
scientists to obtain millions of these cells in a
single tissue culture flask, making something
once rare and precious now readily available to
researchers. It is worth noting here the striking
parallel to recombinant DNA and monoclonal
antibody technologies, both of which have
amplified rare and precious biological entities.
Like those technologies, ES cell technology may
well be transformative in opening scientific
arenas that to date have been closed.
Characteristics & types of Human Stem Cells
Possible Sources of Stem Cells
1. Embryos created via IVF (for infertility
treatment or for research purposes)
2. Embryos or fetuses obtained through
elective abortion
3. Embryos created via SCNT (somatic
cell nuclear transfer, or cloning)
4. Adult tissues (bone marrow, umbilical
cord blood)
Stem Cells from Embryos or Fetal Tissue.
Embryonic stem cells were first isolated from
mouse embryos in 1981. Animal embryos were
the only source for research on embryonic stem
cells until November 1998, when two groups of
U.S. scientists announced the successful
isolation of human embryonic stem cells. One
Fig: In vitro culturing of stem cells
2
group, at the University of Wisconsin, derived
stem cells from one-week-old embryos produced
via in vitro fertilization (IVF).1 The work is
controversial, in the opinion of some individuals,
because the stem cells are located within the
embryo and the process of removing them
destroys the embryo. The second group, at Johns
Hopkins University, derived cells with very
similar properties from five- to nine week-old
embryos or fetuses obtained through elective
abortion. Both groups reported the human
embryos or fetuses were donated for research
following a process of informed consent. The
cells were then manipulated in the laboratory to
create embryonic stem cell lines that may
continue to divide for many months to years.
Stem Cells from cloning. Another potential
source of embryonic stem cells is somatic cell
nuclear transfer (SCNT), also referred to as
cloning. In SCNT the nucleus of an egg is
removed and replaced by the nucleus from a
mature body cell, such as a skin cell. The cell
created via SCNT is allowed to develop for a
week and then the stem cells are removed. In
1996, scientists in Scotland used the SCNT
procedure to produce Dolly the sheep, the first
mammalian clone.4 In February 2004, Korean
scientists announced that they had created human
embryos via the SCNT process and had
succeeded in isolating human stem cells from a
cloned embryo. This development and the
unsubstantiated announcement by Clonaid in
December 2002 of the birth of a cloned child
have contributed to the controversy over research
on human embryos. The isolation, culture, and
partial characterization of stem cells isolated
from human embryos were published in
November of 1998. The ability of the cells to
maintain their pluripotent character even after 4
to 5 months of culturing was demonstrated.
embryonic stem cells, animal experiments on
embryonic germ cells have been limited. In
November of 1998, the isolation, culture, and
partial characterization of germ cells derived
from the gonadal ridge of human tissue obtained
from abortuses were reported. These experiments
showed that these EG cells are capable of
forming the three germ layers that make all the
specific organs of the body. There are fewer data
from animal EG cell experiments than from ES
cell experiments, but it is generally assumed that
the range of potential fates will be relatively
limited compared to ES cells, because the EG
cells are much further along in development (EG
are 5-9 weeks old as opposed to EC which are 5
days). Fetal tissue may provide committed neural
progenitors, but the feasibility of large scale
sourcing and manufacturing of products utilizing
such cells is under research. Furthermore, the
behavior of these cells in vivo is not well
understood; significant research will be required
to avoid unwanted outcomes, including ectopic
tissue, tumor induction, or other abnormal
development.
Fig: Stem cell cultivation and harvesting in vitro
C. Human adult stem cells (ASC). Stem cells
obtained from adult organisms are also the focus
of research. There have been a number of recent
publications on adult stem cells from a variety of
different sources, such as bone marrow. From
post-embryonic development through the normal
life of any organism, certain tissues of the body
require stem cells for normal turnover and repair.
Stem cells that are found in developed tissue,
regardless of the age of the organism at the time,
are referred to as adult stem cells. The most wellknown examples of this are the hematopoietic
stem cells of bone marrow. More recently,
mesenchymal stem cells (MSC) required for the
maintenance of bone, muscle, and other tissues
have been discovered. Adult stem cells are
multipotent; the number of tissues that they can
regenerate
compares
poorly
with
the
pluripotency of embryonic stem cells and
embryonic germ cells. However, the MSC is in
B. Human Embryonic Germ Cells (hEGC).
Embryonic germ cells are derived from
primordial germline cells in early fetal tissue
during a narrow window of development. Unlike
3
fact an excellent example of the potential for use
of stem cells in human therapeutic procedures.
MSCs are capable of differentiating into bone,
cartilage, muscle, fat, and a few other tissue
types. Their use for bone and cartilage
replacement is undergoing final phase of clinical
trials at the present time.
Adult-derived stem cell therapies will
complement, but cannot replace, therapies that
may be eventually obtained from ES cells. They
do have some advantages. For example, adult
stem cells offer the opportunity to utilize small
samples of adult tissues to obtain an initial
culture of a patient’s own cells for expansion and
subsequent implantation (this is called an
autologous transplant). This process avoids any
ethical or legal issues concerning sourcing, and
also protects the patient from viral, bacterial, or
other contamination from another individual.
With proper manufacturing quality controls and
testing, allogeneic adult stem cells (cells from a
donor) may be practical as well. Already in
clinical use are autologous and allogeneic
transplants of hematopoietic stem cells that are
isolated from mobilized peripheral blood or from
bone marrow by positive selection with
antibodies. In general, there is less ethical
concern over their initial source. Additionally,
since they normally differentiate into a narrower
set of cell types, directing them to a desired fate
is more straightforward. However, many cells of
medical interest cannot, as of yet, be obtained
from adult-derived cell types. Production of large
numbers of these cells is much more difficult
than is the case for ES cells. Based upon our
present knowledge base, it appears unlikely that
human adult stem cells alone will provide the
entire necessary cell types required for the most
clinically important areas of research. Adult stem
cells may not be as long lived or capable of as
many cell divisions as embryonic stem cells.
Also, adult stem cells may not be as versatile in
developing into various types of tissue as
embryonic stem cells, and the location and rarity
of the cells in the body might rule out safe and
easy access. For these reasons, many scientists
argue that both adult and embryonic stem cells
should be the subject of research, allowing for a
comparison of their various capabilities.
processed, tested for diseases and then cryopreserved under liquid nitrogen at -1920 C. This
is called cord blood banking and is very rich
source (10 times more than bone marrow) of
stem cells. These stem cells are not as
undifferentiated and as totipotent as the ESC or
EGC, but are pluripotent enough to create
different tissues, more particularly the
hematopoietic stem cells. These can be used at
later stage in life of the same baby to treat
disease (autologous stem cell transplant) or can
be donated to any family member or unrelated
donor for therapeutic use (allogeneic stem cell
transplant). This umbilical cord stem cell
banking discussed below in detail because this is
entirely a separate field of stem cell research.
E. Amniotic fluid stem cells (AFSC). Recently
in January 2007, scientists were able to
successfully harvest stem cells from the amniotic
fluid of the growing fetus in Utero by
amniocentesis (a clinically accepted procedure to
collect amniotic fluid for clinical purposes).
Though the concentration of stem cells in this
fluid is low, it has the great advantage of
obtaining stem cells easily with out any ethical
or legal issues.
The Clinical Potentials for Stem Cell Products
The economic and psychological tolls of chronic,
degenerative, and acute diseases in the entire
world over are enormous. It has been estimated
that up to 200 million people suffer from such
diseases; thus, virtually every citizen is affected
directly or indirectly. The total costs of treating
diabetes, for example is approaching $100
billion in the United States alone. As more
research takes place, the developmental potential
of different kinds of stem cells will become
better understood. As the science is understood
now, adult stem cells are limited in their
potential to differentiate. Embryonic germ cells
have a great differentiation capacity, and
embryonic stem cells are thought to be able to
differentiate into almost any tissue. Thus,
different types of stem cells could have different
applications. Umbilical stem cells can be very
rich source for stem cell transplant and may
better serve in the treatment of hematopoietic
diseases and cancers than bone marrow
transplants (BMT). Below is a discussion of
potential stem cell applications.
D. Umbilical cord blood stem cells (UCSC).
Immediately after the delivery of the baby and
umbilical cord section, the remaining blood from
the placenta and the umbilical cord (other wise
would be discarded as biological waste along
with placenta) will be carefully collected,
Potential Applications of Stem Cell Research.
Stem cells provide the opportunity to study the
growth and differentiation of individual cells into
4
tissues. Understanding these processes could
provide insights into the causes of birth defects,
genetic abnormalities, and other disease states. If
normal development were better understood, it
might be possible to prevent or correct some of
these conditions. Stem cells could be used to
produce large amounts of one cell type to test
new drugs for effectiveness and chemicals for
toxicity. Stem cells might be transplanted into
the body to treat disease (diabetes, Parkinson’s
disease) or injury (e.g., spinal cord). The
damaging side effects of medical treatments
might be repaired with stem cell treatment. For
example, cancer chemotherapy destroys immune
cells in patients, decreasing their ability to fight
off a broad range of diseases; correcting this
adverse effect would be a major advance. Before
stem cells can be applied to human medical
problems, substantial advances in basic cell
biology and clinical technique are required. In
addition, very challenging regulatory decisions
will be required on the individually created tissue
based therapies resulting from stem cell research.
Such decisions would likely be made by the
Center for Biologics Evaluation and Research
(CBER) of the Food and Drug Administration
(FDA). The potential benefits mentioned above
would be likely only after many more years of
research. Technical hurdles include developing
the ability to control the differentiation of stem
cells into a desired cell type (like a heart or nerve
cell) and to ensure that uncontrolled
development, such as a cancerous tumor, does
not occur. If stem cells are to be used for
transplantation, the problem of immune rejection
must also be overcome. Some scientists think
that the creation of many more embryonic stem
cell lines will eventually account for all the
various immunological types needed for use in
tissue transplantation therapy. Others envision
the eventual development of a “universal donor”
type of stem cell tissue, analogous to a universal
blood donor. However, if the SCNT technique
(cloning) was employed using a cell nucleus
from the patient, stem cells created via this
method would be genetically identical to the
patient, would presumably be recognized by the
patient’s immune system, and thus would avoid
any tissue rejection problems that could occur in
other stem cell therapeutic approaches. Because
of this, many scientists believe that the SCNT
technique may provide the best hope of
eventually treating patients using stem cells for
tissue transplantation. The stem cells cultured &
harvested can be programmed to differentiate in
to various cell types by special ‘recipes’. See fig.
Examples of Treatments for Major Diseases
Type 1 Diabetes. Type 1 Diabetes Mellitus is an
autoimmune disease characterized by destruction
of insulin producing cells in the pancreas.
Current efforts to treat these patients with human
islet transplantation in an effort to restore insulin
secretory function (obtained from human
pancreas) are limited severely by the small
numbers of donor pancreatic cells available each
year combined with the toxicity of
immunosuppressive drug treatments required to
prevent graft rejection. Pluripotent stem cells,
instructed to differentiate into a particular
pancreatic cell called a beta cell, could overcome
the shortage of therapeutically effective material
to transplant. They also afford the opportunity to
engineer such cells to effectively resist immune
attack as well as graft rejection.
Nervous System Diseases. Many nervous system
diseases result from loss of nerve cells. Mature
nerve cells cannot divide to replace those that are
lost. Thus, without a “new” source of
functioning nerve tissue, no therapeutic
possibilities exist. In Parkinson’s disease, nerve
cells that make the chemical dopamine die. In
Alzheimer’s disease, cells that are responsible
for the production of certain neurotransmitters
die. In amyotrophic lateral sclerosis, the motor
nerve cells that activate muscles die. In spinal
cord injury, brain trauma, and even stroke, many
different types of cells are lost or die. In multiple
sclerosis, glia, the cells that protect nerve fibers
are lost. Perhaps the only hope for treating such
individuals comes from the potential to create
new nerve tissue restoring function from
5
pluripotent stem cells. Remarkably, human
clinical experiments have demonstrated the
potential effectiveness of this approach to
treatment. Parkinson’s patients have been treated
by surgical implantation of fetal cells into their
brain with benefit. More complex experiments
have already been successfully conducted in
rodent models of Parkinson’s. Similar
approaches could be developed to replace the
dead or dysfunctional cells in cortical and
hippocampal brain regions that are affected in
patients with Alzheimer’s.
More importantly, success would permit use of
very toxic (and effective) chemotherapeutic
regimens that could not currently be utilized for
lack of an ability to restore marrow and immune
function.
Uses in Research
Much is left to be discovered and understood in
all aspects of human biology. What have been
frequently lacking are the tools necessary to
make the initial discoveries, or to apply the
knowledge of discoveries to the understanding of
complex systems. These are some of the larger
problems in basic and clinical biology where the
use of stem cells might be the key to
understanding.
Primary Immunodeficiency Diseases.
Pluripotent stem cells could be used in treatment
of virtually all primary immunodeficiency
diseases. Presently, there are more than 70
different forms of congenital and inherited
deficiencies of the immune system that have
been recognized. These are among the most
complicated diseases to treat with the worst
prognoses. Included here are diseases such as
severe combined immunodeficiency disease (the
“bubble boy” disease), Wiskott - Aldrich
syndrome, and the autoimmune disease lupus.
The immune deficiencies suffered as a result of
acquired immune deficiency syndrome (AIDS)
following infection with the human immunodeficiency virus are also relevant here.14 These
diseases are characterized by an unusual
susceptibility to infection and often associated
with anemia, arthritis, diarrhea, and selected
malignancies. However, the transplantation of
stem cells reconstituted with the normal gene
could result in restoration of immune function
and effective normalization of life span and
quality of life for these people.
A new window in human developmental biology.
The study of human developmental biology is
particularly constrained by practical and ethical
limitations. Human ES cells may allow scientists
to investigate how early human cells become
committed to the major lineages of the body;
how these lineages lay down the rudiments of the
body’s tissues and organs; and how cells within
these rudiments differentiate to form the myriad
functional cell types which underlie normal
function in the adult. The knowledge gained will
impact many fields. For example, cancer biology
will reap an especially large reward because it is
now understood that many cancers arise by
perturbations of normal developmental processes.
The availability of human ES cells will also
greatly accelerate the understanding of the
causes of birth defects and thus lead directly to
their possible prevention.
Models of human disease that are constrained
by current animal and cell culture models.
Investigation of a number of human diseases is
severely constrained by a lack of in vitro models.
A number of pathogenic viruses including
human immunodeficiency virus and hepatitis C
virus grow only in human or chimpanzee cells.
ES cells might provide cell and tissue types that
will greatly accelerate investigation into these
and other viral diseases. Current animal models
of neurodegenerative diseases such as
Alzheimer’s disease give only a very partial
representation of the disease’s process.
Diseases of Bone and Cartilage. Stem cells,
once appropriately differentiated, could correct
many diseases and degenerative conditions in
which bone or cartilage cells are deficient in
numbers or defective in function. This holds
promise for treatment of genetic disorders such
as osteogenesis imperfecta and chondrodysplasias. Similarly, cells could be cultivated
and introduced into damaged areas of joint
cartilage in cases of osteoarthritis or into large
gaps in bone from fractures or surgery.
Cancer. At the present time, bone marrow stem
cells, representing a more committed stem cell,
are used to rescue patients following high dose
chemotherapy.
Complete
and
functional
restoration will be required if, for example,
immune/vaccine anticancer therapy is to work.
Transplantation. Pluripotent stem cells could be
used to create an unlimited supply of cells,
tissues, or even organs that could be used to
restore function without the requirement for
toxic immuno-suppression and without regard to
6
tissue matching compatibility. Such cells, when
used in transplantation therapies, would in effect
be suitable for “universal” donation. Bone
marrow transplantation, a difficult and expensive
procedure associated with significant hazards,
could become safe, cost effective, and be
available for treating a wide range of clinical
disorders, including aplastic anemia and certain
inherited blood disorders. This would be
especially important in persons who lost marrow
function from toxic exposure, for example to
radiation or toxic agents. Growth and transplant
of other tissues lost to disease or accident, for
example,
skin,
heart,
nervous
system
components, and other major organs, are
foreseeable.
Gene Therapy. In gene therapy, genetic material
that provides a missing or necessary protein, or
causes a clinically-relevant biochemical process,
is introduced into an organ for a therapeutic
effect. For gene-based therapies (specifically,
those using DNA sequences), it is critical that
the desired gene be introduced into organ stem
cells in order to achieve long-term expression
and therapeutic effect. Techniques for delivering
the therapeutic DNA have been greatly improved
since the first gene therapy protocol almost 10
years ago. Besides delivery problems, loss of
expression or insufficient expression is an
important limiting factor in successful
application of gene therapy and could be
overcome by transferring genes into stem cells.
Fig: Germline Engineering using all 3 techniques
Spiritual and Religious Contexts
Two broad and somewhat opposing themes
characterize the response of most religious
communities and traditions to the promising new
biomedical technology that stem cell research
represents. On the one hand, there is a moral
commitment to healing and to relieving suffering
caused by injury and illness. Because of this
commitment, most religious communities
applaud the promise of stem cell research for
enhancing scientific understanding of human
development; for probing the cellular origins of
cancer, diabetes, spinal cord injury, arthritis, and
a host of other lethal or disabling illnesses and
conditions; for developing more effective
pharmacological drugs; and for pursuing
successful tissue and organ transplant technology.
On the other hand, most traditions also warn that
human beings are not God. Humans lack
omniscience and our pursuits are often tainted by
selfishness. With regard to stem cell research,
this suggests the need to be cautious in pursuing
the promise of this research and to strive to
anticipate and minimize its potential harms and
misuses. These include direct harms to the
donors of the tissues and embryos from which
stem cells may be derived and harms to future
research subjects exposed to the unknown risks
of stem cell implants. It also includes possible
longer-term harms to society ranging from
damage to our respect for the sanctity of human
life to inequities resulting from the appropriation
Fig: Genetic Engineering using viral vectors
Germline Engineering
A further advanced step would be to combine all
the available technologies such as 1.Stem cell
harvesting 2.Genetic engineering and 3.Cloning
or SCNT. This is called Germline Engineering
and it can be used to obtain Designer Babies means babies that will have all the predefined
features and characters. Isn’t it a marvel? Are we
not interfering with random variations created by
nature in giving the wide biological variation?
This is very useful to weed out genetically
mediated diseases in the progeny. (See figure)
7
or privatization of a resource with great potential
to benefit everyone.
Beyond these two broadly shared themes, there
is significant disagreement among American
religious communities over some of the specific
moral issues raised by stem cell research. The
most medically promising stem cells, with a
capacity to differentiate into any of the human
body’s cell types, are derived either from the
inner cell mass of pre-implantation embryos (ES
cells) or from the gonadal tissue of aborted
fetuses (EG cells). Both of these sources involve
extraction and manipulation of cells from human
embryos or fetuses. This raises issues of
fundamental importance for some religious
communities and can profoundly engage the
conscience of Americans. There are two
principal areas of disagreement. One concerns
the question of whether it is ever morally
appropriate to destroy an embryo and whether
the benefits of research provide a justification for
doing so. At issue here is the question of whether
the human embryo (or fetus in the case of EG
cells) possesses significant moral status and must
be protected from harm. Among those who
answer this in the affirmative, a second question
and some further disagreements arise. This is the
question of whether researchers who have played
no part in the destruction of an embryo or fetus
may ethically utilize cellular materials produced
in these ways. This is the question of when, if
ever, it is morally permissible to cooperate with
or benefit from what some persons regard as evil
acts. The first of these questions is among the
most controversial in our society. It is note
worthy that, despite these differences, all these
positions can support research that does not
involve the use of embryonic or fetal cells, that is
to say, adult stem cell research. Opponents of
abortion also support the use of fetal tissues
when these result from stillbirths or miscarriages.
They object only to the deliberate destruction of
fetuses or embryos. Unfortunately, these zones
of agreement do not include some promising
areas of stem cell research, those involving the
use of cells obtained from embryos (ES cells), or
from deliberately aborted fetuses (EG cells). The
fact that much basic research needs to be done in
the area of human embryonic development
suggests that both ES and EG cells will continue
to play an important role in future research
endeavors. Where germ cells are concerned,
spontaneous abortions or stillbirths are a poor
source of the tissue, both because the collection
of the tissue requires substantial preparation, the
critical time period is of short duration, and
because, with spontaneous abortions particularly,
this tissue is likely to suffer from genetic
abnormalities. While continuing research efforts
must be made to understand the biology of
alternative sources of such cells, adult stem cells
cannot entirely replace either EG and ES cells
because much basic research needs to be done in
the area of early human embryonic development
for which EG and ES cells are required.
Ethical and Moral Concerns
The Moral Status of Human Stem Cells
Human embryonic germ (EG) cells are derived
from the gonadal ridge tissue of an aborted fetus
within five to eight weeks after conception. The
procedure is analogous to the harvesting of
organs from a cadaver. Here the ethical issue is
not so much the status of the aborted fetus. The
ethical status of human embryonic stem cells
partly hinges on the question of whether they
should characterize as embryos or special body
tissue.
Moral issues related to sources of Stem Cells
At present, there are three possible sources of
stem cells: adult stem cells derived from
pediatric or adult donors; embryo germ cell stem
cells (EG cells) derived from aborted fetuses;
and embryonic stem cells (ES cells) derived from
disaggregated pre-implantation embryos. The
first of these sources poses no special ethical
problems for the majority of people. Individuals
who do not object to induced abortion will be
less concerned about the use of EG cells than
those opposed to abortion. The least ethically
problematic case would be to harvest stem cells
from spontaneously aborted fetuses. There are,
however, several obstacles to obtaining useful
EG cells from spontaneously aborted tissue.
Foremost is the problem of the harvesting
healthy cells from fetuses. Results from several
studies indicate that about 60% of all
spontaneous abortions arise as a result of specific
fetal anomalies; specific chromosomal abnormalities were identified in about 20% of those.
While stem cells with damaged genetic
complements may be useful for a limited number
of experiments, they are unlikely to be the basis
of experiments leading to useful “normal” tissue.
Finally, there is the matter of timing. EG cells
can only be obtained during a narrow
developmental phase, within the first eight
weeks after conception. Most spontaneous
abortions that occur during this period do not
take place in a hospital or clinic where the tissue
can be readily obtained. Some people holding
8
this view may also accept the deliberate creation
of embryos for this purpose, while others would
only permit the use of so-called “spare embryos”
remaining from infertility procedures.
The second and third source noted above (i.e.,
embryonic stem cells or embryonic germ cells
obtained from elective abortions), however, raise
special moral questions for those who regard
either abortion or the destruction of early
embryonic life as morally wrong. Can such
people support or become involved in research
using EG or ES cells when these cells are
derived from what they regard as the morally
unacceptable killing of a fetus or embryo? It is
clear that not all use of goods produced by
wrongful acts is immoral. For example, medical
researchers routinely employ tissues of people
who are victims of murder or other wrongful acts.
pregnancy as necessary to achieve their goals.
Often, they end up with more embryos than they
need to use. Persons with excess embryos have
the option of donating them to other infertile
couples, destroying them, or donating them for
research purposes.
Umbilical Cord Blood Banking
Cord blood, which is also called "placental
blood," is the blood that remains in the umbilical
cord and placenta following birth and after the
cord is cut. Cord blood is routinely discarded
with the placenta and umbilical cord. The baby's
umbilical cord blood is a valuable source of stem
cells, which are genetically unique to that baby
and family. The first cord blood transplant was
performed in 1988. Since then, more than 4,000
transplants have occurred. The opportunity for
expectant families to collect and store their
newborn's umbilical cord blood stem cells has
only been widely available since late 1995.
Currently, thousands of parents are taking
advantage of this once-in-a-lifetime opportunity.
Sources of Stem Cells and Guidelines for Use
Securing stem cells for research, whether from
children, adults, aborted fetuses, or embryos,
must be done under conditions of the most
rigorous integrity for several reasons. These are
to protect the interests of the donors, to reassure
the public that important boundaries are not
being overstepped, to enable those who are
ethically uncomfortable with elements of this
research to participate to the greatest extent
possible, and to assure the highest quality of
research and outcomes.
As already noted, there are three different types
of stem cells, derived from three different
sources. Obtaining the first type, adult stem cells,
presents no new ethical problems. Whether from
adults or from children, protection of donors
comes under the heading of research with human
subjects, where adequate protection and
regulation exist. The second source is cells
derived from aborted fetuses. Research with fetal
tissue of all types is already ongoing in both the
private and public sectors. The third source, preimplantation embryos, requires the greatest care.
Human embryonic stem cells should be derived
from two sources. The first are so-called “spare”
embryos, those remaining after a couple has
completed their family. The second are embryos
that are not of sufficient quality to be candidates
for transfer to the uterus. Persons create embryos
through in vitro fertilization with the intent of
transferring one or more of them to the uterus,
the hoped for outcome being a successful
pregnancy and a healthy baby. Because eggs
cannot be frozen but embryos can, persons using
IVF usually aim to produce a group of stored,
frozen embryos to support as many attempts at
The collection can only take place at the time of
delivery and is normally performed by your
caregiver. More than 18,000 caregivers have
collected cord blood so far at more than 2,500
hospitals and birthing centers in the U.S., and in
more than 60 countries. The cord blood is
collected after the baby has been born and the
umbilical cord has been clamped and cut. The
collection is painless, easy, and safe for mother
and baby. The average time for cord blood
collection is about 5 minutes. A collection kit for
the baby's cord blood stem cells will be used
which contains all the items the caregiver will
need to collect the cord blood. It can be collected
both during vaginal and C’ Section deliveries
Currently, cord blood stem cells are primarily
used in transplant medicine to regenerate a
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patient's blood and immune system after they
have been treated with chemotherapy and/or
radiation to destroy cancer cells. At the same
time the chemotherapy and radiation destroys the
cancer cells in a patient, they also destroy stem
cells. Therefore, an infusion of stem cells or a
stem cell transplant is performed after the
chemotherapy and/or radiation treatment. The
stem cells then migrate to the patient's bone
marrow where they multiply and regenerate all
of the cells to create a new blood and immune
system for the patient. The promise of using
stem cells for medical treatments has been the
focus of research projects that are showing
encouraging results. Cord blood stem cells have
been "triggered" to differentiate into neural cells,
which could lead to treatments for diseases such
as Alzheimer's and Parkinson's. They have also
proven their ability to turn into blood vessel cells,
which could some day benefit treatments for
heart disease, allowing patients to essentially
"grow their own bypass." Umbilical cord blood
stem cells are the "youngest," safely available
stem cells and they are the product of another
miracle -a live birth. Freezing these cells
essentially stops the clock and prevents aging &
damage that may occur to the cells later in life.
Cord blood banking facilities in India now
Cord blood banking, an alien concept till a few
years ago in India is becoming popular, courtesy
a few private companies that have begun
operations. There are two types of banks; family
banks (for one's own family's use) and public
donor banks (unrelated or non-family use i.e.
"public"). Every parent has the option of saving
cord blood for their baby and family, or may
donate their baby's cord blood stem cells. Ethnic
minorities and families of mixed ethnicity have
greater difficulty finding stem cell donors when
needed. Storing cord blood in private banks as a
`biological insurance' comes at a price.
The first cord blood repository in India was
established by the company Reliance Life
Sciences (RLS), which incorporated in 2001.
They have ReliCord-S for private banking and
ReliCord-A for public banking. National network
of public cord blood banks by RLS was formed
in 2005. The Indian government signed a deal
with the Korean company Histostem to set up a
bank in Mumbai, with additional centres planned
for Delhi, Chennai and Kolkata. Ultimately,
these centres will offer regenerative stem cell
therapies, like the Histostem hospital in Korea
for medical tourists. The government has a 10%
equity stake in the venture. Donors to the
program must pay Rs. 12,000, but in return are
promised matching cells should they be needed.
Bone marrow is difficult to match between the
donor and recipient because a "perfect match" is
usually required. Cord blood immune cells,
however, are less mature than in bone marrow
and can be successfully used even when there is
only a half-match. This means there is more
opportunity for transplants between family
members when cord blood is stored. Some
studies have shown that overall survival rates for
related transplants are more than double that of
transplants from unrelated donors. Banking cord
blood ensures that these stem cells can be
immediately available if they are needed for
treatment. Early treatment of many illnesses can
minimize disease progression. Overall, patients
who receive cord blood transplants from a
related donor experience significantly less Graft
vs. Host Disease (GVHD), a transplant rejection
that is the leading cause of death in stem cell
transplant patients.
The first strictly private cord blood bank in India
is LifeCell, owned by Asia Cryo-Cell Pvt. Ltd
(ACCPL), an affiliate of the American cord
blood bank Cryo-Cell International that is
located in Chennai and began operations in late
2004. By April 2006, LifeCell had 12 collection
centres in India and intends to expand into
Malaysia and Dubai. A new centre exclusively
for stem cell transplants will be operational in
Chennai in 2006. The transplant centre is a joint
venture of Lifecell, which will invest Rs 150
million, and Sri Ramachandra Medical Centre,
which will provide 15,000 sq. ft. of space in their
hospital in Chennai.
As of January 2006, Reliance, Histostem, and
LifeCell were the only 3 companies licensed by
the Indian Council of Medical Research (ICMR),
to store cord blood stem cells. However, during
2005, an explosion of foreign companies
announced plans for cord blood banks in India.
Fig: The final product of cord blood for banking
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The rationale for public cord blood banking
Private cord blood banking centres are built
around the possibility of use either by the same
child at a later date or by siblings who are either
already sick or may require cord blood in case
they have genetic, haematologic or oncology
disorders. Storing cord blood in these private
cord blood banks as a `biological insurance' for
its possible use by the same child or by its
siblings, comes at a price. It would cost
Rs.60,000 to store cord blood for 21 years in
liquid nitrogen facilities. Public cord blood
banking is another option where parents `donate'
the cord blood of their baby to a central facility
for use by anybody who needs it. The child or its
family members no longer have the right to
claim it when the need arises and have to pay
like any other individual.
Despite the need for payment by an individual
who has donated cord blood, public cord blood
banking makes better sense. We foresee a day in
which most patients will volunteer their cord
blood to such banks. Those who do so will value
real public benefits against the sometimes,
exaggerated claims of individual benefits
advanced by private cord blood banks.
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Apollo Specialty Hospital, Madras,
Apollo Hospital, Global Hospitals,
NIMS, Hyderabad
Christian Medical College, Vellore
Narayana Hruduyalaya , Bangalore
R&R Army Hospital, New Delhi
AIIMS , New Delhi
Inlaks Hospital, Pune
Armed Forces Medical College, Pune
Sanjay Gandhi PGIMS, Lucknow
Emotional marketing of private banking
The emotional marketing resorted to by private
cord blood banks perforce compels them not to
reveal the many shortcomings or disadvantages.
For instance, the private companies that dangle
the `biological insurance' carrot while selling the
concept to expectant parents never reveal the
chances of a child ever needing cord blood at a
later date. No accurate estimates exist of the
likelihood of children needing their own stored
cells. The range of available estimates is from
1:1,000 to 1:2,00,000. Empirical evidence that
children will need their own cord blood for
future use is lacking. It becomes relevant when a
family member already has a current or potential
need for stem cell transplantation. All these build
a strong case for setting up public cord blood
banks. The public bank run by Reliance Life
Sciences in Mumbai is the only one of its kind.
There are 14 such public banks in the U.S. and
30 or more worldwide.
Tests done on the umbilical cord blood
HLA typing is not done routinely while banking.
It is done only before giving Stem Cell transplant.
The diseases are screened by testing for
 Syphilis
 HIV Ag and Ab
 Hepatitis B and C
 ALT
 Malaria
 Leptospirosis
 HTLV 1 and 2, CMV, EB Virus
 Blood grouping, Rh typing and CD 34
count
Recommended and used resources
 www.stemcells.nih.gov
 www.stemcellforum.org
 www.cordbloodforum.org
 www.marrow.org
 www.aaas.org
 www.relbio.com
 www.lifecell.com
 www.jdrf.org
 www.drsarma.in
Regenerative medicine. Stem cell transplants are
used to successfully treat the following diseases:
 Permanent repair of failing organs
 Cardiomyocytes for heart disease
 Angiogenesis for coronary heart disease
 Islet cells for diabetes
 Neural cells for Parkinson’s
 Blood cells for cancer
 Chondrocytes for osteoporosis
 Keratinocytes for burns
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The author of this article is a Senior Consultant
Physician and Chest Specialist having private
practice. He is a visiting consultant at Billroth
Hospitals, Chennai. Please visit www.drsarma.in
for free download of many CMEs on various
interesting topics. Dr. Sarma is available as a
resource person and faculty for CMEs. Please
contact him (0) 9380521221 or (0) 9894060593.
Stem Cell therapy centers in India
 Tata Memorial Hospital, Mumbai
 Adyar Cancer Centre, Madras
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