What are Stem Cells?
Stem cells are a class of undifferentiated cells that are able to
differentiate into specialized cell types. Commonly, stem cells come
from two main sources:
- Embryos formed during the blastocyst phase of embryological development (embryonic stem cells) and
- Adult tissue (adult stem cells).
Both types are generally characterized by their potency, or potential to
differentiate into different cell types (such as skin, muscle, bone,
etc.).
Adult stem cells
Adult or somatic stem cells exist throughout the body after embryonic
development and are found inside of different types of tissue. These
stem cells have been found in
tissues such as the brain, bone marrow, blood, blood vessels, skeletal
muscles, skin, and the liver. They remain in a quiescent or non-dividing
state for years until activated
by disease or tissue injury.
Adult stem cells can divide or self-renew indefinitely, enabling them to
generate a range of cell types from the originating organ or even
regenerate the entire original organ.
It is generally thought that adult stem cells are limited in their
ability to differentiate based on their tissue of origin, but there is
some evidence to suggest that they can
differentiate to become other cell types.
Embryonic stem cells
Embryonic stem cells are derived from a four- or five-day-old human
embryo that is in the blastocyst phase of development. The embryos are
usually extras that have been
created in IVF (in vitro fertilization) clinics where several eggs are
fertilized in a test tube, but only one is implanted into a woman.
Sexual reproduction begins when a male's sperm fertilizes a female's
ovum (egg) to form a single cell called a zygote. The single zygote cell
then begins a series of divisions,
forming 2, 4, 8, 16 cells, etc. After four to six days - before
implantation in the uterus - this mass of cells is called a blastocyst.
The blastocyst consists of an inner cell mass
(embryoblast) and an outer cell mass (trophoblast). The outer cell mass
becomes part of the placenta, and the inner cell mass is the group of
cells that will differentiate to
become all the structures of an adult organism. This latter mass is the
source of embryonic stem cells - totipotent cells (cells with total
potential to develop into any cell in the
body).
In a normal pregnancy, the blastocyst stage continues until implantation
of the embryo in the uterus, at which point the embryo is referred to
as a fetus. This usually occurs by
the end of the 10th week of gestation after all major organs of the body
have been created.
However, when extracting embryonic stem cells, the blastocyst stage
signals when to isolate stem cells by placing the "inner cell mass" of
the blastocyst into a culture dish
containing a nutrient-rich broth. Lacking the necessary stimulation to
differentiate, they begin to divide and replicate while maintaining
their ability to become any cell type in
the human body. Eventually, these undifferentiated cells can be
stimulated to create specialized cells.
Stem cell cultures
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.
Potency
Stem cells are categorized by their potential to differentiate into
other types of cells. Embryonic stem cells are the most potent since
they must become every type of cell in the
body. The full classification includes:
- 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.
What are stem cells - Video
A video on how stem cells work and develop.
Identification of stem cells
Although there is not complete agreement among scientists of how to
identify stem cells, most tests are based on making sure that stem cells
are undifferentiated and
capable of self-renewal. Tests are often conducted in the laboratory to
check for these properties.
One way to identify stem cells in a lab, and the standard procedure for
testing bone marrow or hematopoietic stem cell (HSC), is by
transplanting one cell to save an individual
without HSCs. If the stem cell produces new blood and immune cells, it
demonstrates its potency.
Clonogenic assays (a laboratory procedure) can also be employed in vitro
to test whether single cells can differentiate and self-renew.
Researchers may also inspect cells
under a microscope to see if they are healthy and undifferentiated or
they may examine chromosomes.
To test whether human embryonic stem cells are pluripotent, scientists
allow the cells to differentiate spontaneously in cell culture,
manipulate the cells so they will differentiate
to form specific cell types, or inject the cells into an
immunosuppressed mouse to test for the formation of a teratoma (a benign
tumor containing a mixture of
differentiated cells).
Research with stem cells
Scientists and researchers are interested in stem cells for several
reasons. Although stem cells do not serve any one function, many have
the capacity to serve any function
after they are instructed to specialize. Every cell in the body, for
example, is derived from first few stem cells formed in the early stages
of embryological development.
Therefore, stem cells extracted from embryos can be induced to become
any desired cell type. This property makes stem cells powerful enough to
regenerate damaged
tissue under the right conditions.
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.
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.
General scientific discovery
Stem cell research is also useful for learning about human development.
Undifferentiated stem cells eventually differentiate partly because a
particular gene is turned on or
off. Stem cell researchers may help to clarify the role that genes play
in determining what genetic traits or mutations we receive. Cancer and
other birth defects are also
affected by abnormal cell division and differentiation. New therapies
for diseases may be developed if we better understand how these agents
attack the human body.
Another reason why stem cell research is being pursued is to develop new
drugs. Scientists could measure a drug's effect on healthy, normal
tissue by testing the drug on
tissue grown from stem cells rather than testing the drug on human
volunteers.
Stem cell controversy
The debates surrounding stem cell research primarily are driven by
methods concerning embryonic stem cell research. It was only in 1998
that researchers from the
University of Wisconsin-Madison extracted the first human embryonic stem
cells that were able to be kept alive in the laboratory. The main
critique of this research is that it
required the destruction of a human blastocyst. That is, a fertilized
egg was not given the chance to develop into a fully-developed human.
When does life begin?
The core of this debate - similar to debates about abortion, for example
- centers on the question, "When does life begin?" Many assert that
life begins at conception, when
the egg is fertilized. It is often argued that the embryo deserves the
same status as any other full grown human. Therefore, destroying it
(removing the blastocyst to extract
stem cells) is akin to murder. Others, in contrast, have identified
different points in gestational development that mark the beginning of
life - after the development of certain
organs or after a certain time period.
Chimeras
People also take issue with the creation of chimeras. A chimera is an
organism that has both human and animal cells or tissues. Often in stem
cell research, human cells are
inserted into animals (like mice or rats) and allowed to develop. This
creates the opportunity for researchers to see what happens when stem
cells are implanted. Many
people, however, object to the creation of an organism that is "part
human".
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.
Stem cell research news
Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our
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This
what are stem cells? information section was written by
Peter Crosta for Medical News Today, and may not be re-produced in any
way without the permission of
Medical News Today.
