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Stem Cells
Stem cells are mother cells that have the potential to become any type of cell in the
body. One of the main characteristics of stem cells is their ability to self-renew or
multiply while maintaining the potential to develop into other types of cells. Stem
cells can become cells of the blood, heart, bones, skin, muscles, brain etc. There
are different sources of stem cells but all types of stem cells have the same
capacity to develop into multiple types of cells.
Stem cells are different from other cells in the body. There are three unique
properties of all stem cells regardless of their source. These include:-
capability of dividing and renewing themselves for long periods
being unspecialized and basic cells
they can give rise to any type of specialized cell because they are
unspecialized

Stem cells (center ones) can develop into any cell type. They are valuable as research tools and
might, in the future, be used to treat a wide range of diseases.

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POTENCY

Totipotent - the ability to differentiate into all possible cell types. Examples are
the zygote formed at egg fertilization and the first few cells that result from the
division of the zygote.
Pluripotent - 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.
Multipotent - the ability to differentiate into a closely related family of cells.
Examples include hematopoietic (adult) stem cells that can become red and
white blood cells or platelets.
Oligopotent - the ability to differentiate into a few cells. Examples include
(adult) lymphoid or myeloid stem cells.
Unipotent - the ability to only produce cells of their own type, but have the
property of self-renewal required to be labeled a stem cell. Examples include
(adult) muscle stem cells.
Embryonic stem cells are considered pluripotent instead of totipotent because they
do not have the ability to become part of the extra-embryonic membranes or the
placenta.

Types of stem cells

Embryonic stem cells
Embryonic stem cells can be derived from the blastocyst stage of an embryo. These
are also called pluripotent cells as they have the capacity to produce all of the
bodys cell types.
The blastocyst is a mostly hollow sphere of cells smaller that a pin head. In its
interior is the inner cell mass with around 30 cells. These cells are cultured in the
laboratory to yield millions of cells.
The embryos used for obtaining these stem cells are obtained from the excess
embryos that couples willingly donate after informed consent and after they have
successfully had their offspring. Embryos that have been fertilized within a womans
body are not used.

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Embryonic stem cells are more flexible and can be made into any type of cell that is
desired. They are generally easier to collect, purify and maintain in the laboratory
than adult stem cells. These cells, however, need to be differentiated into
specialized cells before they can be transplanted or else they may lead to tumors
called teratomas.

Adult stem cells
Adult stem cells are found in certain tissues in fully developed humans. This could
be present in babies, children, adolescents or adults. These stem cells are limited to
producing only certain types of specialized cells.
The primary roles of adult stem cells in the body are to maintain and repair the
tissues in which they are found. These stem cells are also called somatic stem cells
instead of adult stem cells as they may be found in persons of all ages (not just
adults).
Research with adult stem cells began in the 1960s when scientists found that
the bone marrow contains at least two kinds of stem cells the blood cell forming
hematopoietic stem cells and the bone marrow stromal cells that are a cell
population that generates bone, cartilage, fat, and fibrous connective tissue.
Adult stem cells are also found inbrain, peripheral blood, blood vessels, skeletal
muscle, skin and liver. There is a very small number of adult stem cells at these
sites.
Amniotic Stem Cells
These are stem cells found in the amniotic fluid. These stem cells are very active
and can proliferate without feeders. In addition, unlike embryonic stem cells they
do not cause tumors. These can be made into fat cells, bone cells, muscle cells,
blood vessel walls, liver and nerve cells.
Induced Pluripotent Stem Cells
These are not adult stem cells but are created from adult skin cells after genetically
programming them to become pluripotent stem cells.


Difference between embryonic stem cells and adult stem cells
Two basic factors in stem cell research are the difference between embryonic stem
cellsthat proliferate for a year or more in the laboratory without specializing or

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differentiating into different types of cells and adult stem cells that cannot
proliferate without differentiating.
Another baffling factor is the presence of certain triggers and regulators that control
stem cell proliferation and self-renewal.
Stem cells are unspecialized
One of the main properties of stem cells is that they are unspecialized. They are
basic cells. Stem cells do not function like nerve cells, muscle cells, gland cells or
any other specific cell of the body.
Proliferation and specialization
The property of being unspecialized also accompanies the fact that these cells can
divide and renew themselves for long periods.
Normally muscles cells, nerve cells, blood cells and other specialized cells do not
normally replicate themselves but stem cells have the capability to do so. This
replication is called proliferation. Proliferation over months can give rise to millions
of cells. If the resulting cells are unspecialized, self renewal continues for long
periods of time.
The factors that prevent a stem cell from becoming specialized can help in
increasing the effectiveness of the stem cells in proliferation.
Differentiation
When unspecialized stem cells give rise to specialized cells, the process is called
differentiation. Some signals both from within and from outside the cell can trigger
stem cell differentiation.
While signals within the cell are controlled by a cell's genes which are present over
strands of DNA, the external signals for cell differentiation include chemicals from
other cells, contact with neighbouring cells and presence of certain molecules in the
environment.
In 1961, scientists found that adult bone marrow could yield stem cells. This bone
marrow could be coaxed to form all the different types of blood cells. It was not
until 1988 that these cells could be isolated in their pure form. The time lag can be
explained by the fact that adult stem cells are inconspicuous in shape, size, and
function and are present in very small amounts in the tissues. This makes their
identification and isolation into pure cell lines difficult.



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Identification of stem cells
There is a standard battery of tests that can help identify stem cells. For embryonic
stem cells, serial subculturing for many months without differentiation is the first
test that determines capability of long-term self-renewal. The cells are examined
under the microscope to see if they are healthy and remain undifferentiated.
Another important test is to look for presence of a protein called Oct-4 that is
typically made by undifferentiated cells. Oct-4 is a transcription factor that helps
turn genetic switches on or off. Chromosomes of the cells are also examined to look
for damage if any.
For many adult stem cells molecular markers, use of molecules that recognize and
attach to specific surface proteins and can fluoresce under certain wavelengths of
light, can help in identification.

Culturing cell lines and stimulating differentiation
Obtained stem cells from the inner cell mass of a blastocyst or from adult stem
cells are more often than not present in very small amounts. These are then
cultured in the laboratory to make them proliferate and multiply. This helps in
actual use of the stem cells in research and in therapeutics.
Cell culture refers to the growth and maintenance of cells in a controlled laboratory
environment outside the organism. For a successful stem cellculture the cells should
be healthy, dividing, and unspecialized for initial and series of subcultures, re-
plating and transplantation onto other fresh culture media. This series of
subcultures may go on for months to yield the desired number of cells.
The stem cell culture is the first step in establishing a stem cell line. A cell line is a
propagating collection of genetically identical cells. Cell lines are important because
they provide a long-term supply of multiplying identical cells that can be used by
more than one scientist in different laboratories for research and development of
new therapeutic methods.
According to the National Academies report Stem Cells and the Future of
Regenerative Medicine (2001), maintaining a healthy stem cell line is the most
challenging part of stem cell research. The report says that Over time, all cell
lineschange, typically accumulating harmful genetic mutations. There is no reason
to expect stem cell lines to behave differently.
After a stable cell line is established, the cells are then coaxed to form specialized
cells. This is brought about spontaneously for adult stem cells and by changing
chemical environments or genetic triggers for embryonic stem cells.
Embryonic stem cells cannot be used before full differentiation as this can lead to a
type of tumor called a teratoma.

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Stem cell cultures

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.
Stem cell lines
Once stem cells have been allowed to divide and propagate in a controlled culture,
the collection of healthy, dividing, and undifferentiated cells is called a stem cell
line. These stem cell lines are subsequently managed and shared among
researchers. Once under control, the stem cells can be stimulated to specialize as
directed by a researcher - a process known as directed differentiation. Embryonic
stem cells are able to differentiate into more cell types than adult stem cells.

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 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.




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Cardiovascular disease treatment
A team of researchers from Massachusetts General Hospital reported in PNAS Early
Edition (July 2013 issue) that they were able to create blood vessels in laboratory
mice using human stem cells.
The scientists extracted vascular precursor cells derived from human-induced
pluripotent stem cells from one group of adults with type 1 diabetes as well as from
another group of healthy adults. They were then implanted onto the surface of
the brains of the mice.
Within two weeks of implanting the stem cells, networks of blood-perfused vessels
had been formed - they lasted for 280 days. These new blood vessels were as good
as the adjacent natural ones.
The authors explained that using stem cells to repair or regenerate blood vessels
could eventually help treat human patients with cardiovascular and vascular
diseases.
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.
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 treatments
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.


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Stem Cell Controversy

There are several ethical issues that are raised while working with stem cells. The
ethical issues were addressed in a 2005 guidelines for research with
human embryonic stem cells by the National Academies. This urges scientists who
work with embryonic stem cells to be responsible, ethical and sensitive in their
work. The guidelines were not legally binding but laid the foundation for stem
cell research principles for many scientists and their laboratories.
Controversy with embryo use
The largest controversy with stem cell research is the use of an embryo. This deals
with the controversies surrounding laws and beliefs regarding contraception,
abortion, and in vitro fertilization.
To obtain embryonic stem cells, researchers use the inner cell mass from the
blastocysts (fertilized eggs) from an in vitro fertilization facility. These blastocysts
are the ones that are excess and donated voluntarily by couples who have been
treated successfully for their infertility. Embryos that have been fertilized within a
womans body are not used. The blastocysts used for science are donated of free
will with informed consent of the couple.
Controversies arise if the embryo is human and whether the embryo has legal and
moral rights. The removal of the inner cell mass prevents the blastocysts from
continuing to develop. Although such blastocysts would likely be discarded and
destroyed by the clinics eventually if not used for research, controversy still
shrouds their use for a scientific purpose.
Some believe that life of a human being begins at the moment of conception and
the embryos deserve protection. In addition, some cultures and religious traditions
do not support the use of human life as a means to some other end despite the end
being a noble one. Yet other cultures support embryonic stem cell research as they
believe that the embryo has a moral right as a human only after a few months of
development.
Controversy with reproductive cloning
Cloning and stem cell research are two different procedures all together. They have
a common link, however, and this is use of a laboratory technique called nuclear
transfer. Using this method scientists can create blastocysts containing stem cells
that are clones of a single adult cell using the genetic material from an adult cell
into an ovum or egg whose nucleus has been removed. This could result in identical
genetic matches of the adult donor leading to a safer alternative to traditional
tissue transplants.

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In 2002, the National Academies issued the report Scientific and Medical Aspects
of Human Reproductive Cloning concluding that human reproductive cloning should
not be practiced as it is dangerous and may fail.
Controversy regarding Human-Animal Chimeras
Chimeras mean organisms that contain cells or tissues from more than one
organism. Ethics steps in when human and animal cells are combined to create
chimeras. For example, human stem cells may be transplanted into a mouse to
check for certain functions (human stem cells making pancreatic cells into a mouse
for example for developing therapies for diabetics).
Chimeras are important for advancing stem cell research to form actual therapeutic
methods and targets. This is because the therapies developed with the stem cells
need to be tried on animals before being tried on humans.
Chimeras with human consciousness and introduction of human stem cells into a
non-human primate (e.g. an ape, chimpanzee etc.) are prohibited by the National
Academies guidelines. Similarly the organization also prohibits introduction of any
animal or human cells into a human blastocyst. Breeding of human-animal
chimeras are also prohibited.
Legal issues
The stem cell debate has risen to the highest level of courts in several countries.
Production of embryonic stem cell lines is illegal in Austria, Denmark, France,
Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden,
and the UK. In the United States, it is not illegal to work with or create embryonic
stem cell lines. However, the debate in the US is about funding, and it is in fact
illegal for federal funds to be used to research stem cell lines that were created
after August 2001.