The day-to-day work that goes
on in the laboratories across the country studying
stem cells begins with developing ways to identify
stem cells, culture cell lines and stimulate stem cells to
differentiate. Once these first steps have been
achieved, work on animals plays an important role in
furthering basic research and developing medical
applications. This work is necessary to form the foundation
of knowledge that will point the way to medical
advances. To address ethical concerns about the destruction of
blastocysts, scientists are trying to find alternatives to using embryos
in stem cell research.
Identifying Stem Cells [top]
As early as 1961, scientists knew that adult bone marrow
contained cells that could make all of the blood
cell types. But it wasn't until 1988 that those stem cells
were isolated as pure populations.
Why did it take so
long? The techniques for identifying stem cells have
only recently been developed. Partly, this is because
adult stem cells are, by their very nature, inconspicuous
in shape, size, and function. They also tend to hide
deep in tissues and are present only in very low numbers,
making their identification and isolation like
finding a needle in a haystack.
How do scientists know when they have found a stem
cell? Every cell displays an array of proteins on its surface;
different cell types have different proteins.
Scientists can use these surface proteins as "markers"
that characterize individual cell types-a type of
"molecular ID." For example, using molecules that
recognize and attach to specific surface proteins and
that can fluoresce under certain wavelengths of light,
scientists can visually tell the difference between a
blood stem cell and a mature white blood cell.
Unfortunately, not all stem cells can now be identified
in this manner because scientists have not yet identified
markers for all stem cell types. Scientists also identify
stem cells by observing their behavior in the
laboratory: stem cells must be able to remain unspecialized
and self-renew for long periods of time.
Scientists believe that there might be more types of
adult stem cells than the handful that have already
been identified, but finding them is a difficult process.
Culturing Cell Lines and Stimulating Stem Cells to Differentiate [top]
Cell culture is a term that refers to the growth and
maintenance of cells in a controlled environment outside
of an organism. A successful stem cell culture is
one that keeps the cells healthy, dividing, and unspecialized.
The culturing of stem cells is the first step in
establishing a
stem cell line—a propagating collection
of genetically identical cells. Cell lines are important
because they provide a long-term supply of multiplying
cells that can be shared among scientists for
research and therapy development.
The National
Academies report
Stem Cells and the Future of
Regenerative Medicine (2001) described some of the
challenges of maintaining cell lines: "Over time, all
cell lines change, typically accumulating harmful
genetic mutations. There is no reason to expect stem
cell lines to behave differently. While there is much
that can be learned using existing stem cell lines, such
concerns necessitate continued monitoring of these
cells as well as the development of new stem cell lines
in the future."
Once they have established a stable stem cell line, scientists
start the process of causing the stem cells to differentiate
into specialized cell types. The cellular environment
in which stem cells naturally reside provides
scientists with clues about how to make
them differentiate in a culture dish. For example,
in the bone marrow, where blood stem cells
reside, bone cells send physical and chemical signals
that tell the blood stem cells when to differentiate.
Scientists are just beginning to understand
these signals and have developed ways to
mimic the natural processes in cell cultures.
Usually, the technology involves adding certain
proteins to the cell culture and, in some cases,
introducing specific genes into the stem cells.
It will be essential that scientists are sure that
stem cells have fully differentiated before they
can use them for medical applications. If
completely undifferentiated stem cells (such as
embryonic stem cells) are implanted directly into
an organism, they can cause a type of tumor
called a teratoma, which scientists have observed
in experiments using mice. Semi-specialized
adult stem cells and differentiated cells derived
from embryonic stem cells are unlikely to cause
teratomas.
The Role of Animals in Stem Cell Research [top]
For medical research, as well as for research that
explores the basic processes in the development
of organisms and diseases, scientists often rely on
animals. Implanting human cells into animals
such as mice has long been common practice in
order to test the safety and effectiveness of new
drugs, procedures, and medical devices before
clinical testing in human volunteers.
For stem
cell research, scientists use animals to make sure
the stem cells are able to incorporate into the tissue,
do not cause any harmful consequences,
and function in concert with the rest of the body.
For example, before using stem cells to replace
the pancreatic cells that are destroyed by type I
diabetes in humans, scientists will transplant
human stem cells into a mouse to see whether
the stem cells yield healthy, insulin-producing
cells. If their methods prove successful in mice,
scientists may eventually apply the technology to
developing treatments for diabetes in humans.
Animal studies can also reveal how human
cells differentiate during normal development.
For example, scientists may implant human
stem cells into a developing mouse to observe
the processes involved in building and organizing
the different tissue types that make up
the human body.
Scientists can also trace the
development and progression of certain diseases
within an animal. By implanting human
stem cells that lead to a particular disease into
a mouse blastocyst, scientists can observe
when and how the afflicted cells begin to show
signs of disease and can test drugs that might
prevent that process.
Organisms that contain cells or tissues from another
individual of the same or a different species are
called
chimeras. A common example of a chimera is
a mouse that has been injected with some human
cells so that it can be used for studying a human disease
or testing a new drug. A person who has had a
blood transfusion or a person who has received a
heart valve transplant from a pig is technically a
chimera, as well. The making of chimeras for research
has unique ethical implications that have been the
topic of discussions among scientists, ethicists and the
public, especially when the chimeras contain both
human and animal cells.
Alternatives to Using Embryos in Stem Cell Research [top]
To address ethical concerns about the destruction of
blastocysts, scientists are trying to find new ways of
obtaining stem cells that behave like embryonic
stem cells but that don't require harming a blastocyst.
As the science progresses, ethical issues surrounding
these alternatives may also arise. Some
possible alternatives include:
- Cells collected from the
morula (MOR-yoo-la), the
developmental stage prior
to the blastocyst. The
morula, a solid ball of
about 16-30 cells, seems
able to sustain the loss of a
few cells without developmental damage so that
the remaining cells can continue to develop.
Cell extraction from the morula is already being
used in some clinics to screen for genetic
disorders in embryos produced by in vitro
fertilization.
Researchers have recently shown
that cells isolated from a mouse morula can give
rise to embryonic stem cells while the remaining
morula cells develop into a healthy mouse.
However, this process may still be morally objectionable
to some because of the chance of harm
to the morula, and because the long-term effects
of removing cells from a morula are not yet
known.
- The creation of embryonic stem cells through a
process called altered nuclear transfer (ANT).
In this variation of the nuclear transfer technique,
scientists create a blastocyst whose genetic
material has been changed so that further
development and implantation into the uterus
is not possible. It aims to create embryo-like
entities that are not truly embryos but that can be
a source of pluripotent stem cells.
ANT, so far only
tested with mouse blastocysts, could allow the
creation of embryonic stem cells without destroying
a viable human blastocyst. Some who object to
embryonic stem cell research support ANT
because the resulting blastocyst could never
develop into a full human being and therefore
would not have the moral status of a human
embryo. However, this procedure is objectionable
to some because they believe that it involves the
creation of an imperfect blastocyst that is designed
to be destroyed.
- Causing an adult cell to act like an embryonic
stem cell. During development, as cells become
more and more specialized, they gradually lose the
ability to turn on the genes that allow embryonic
stem cells to be so versatile. The silencing of
these genes seems to be responsible for keeping
specialized cells specialized and limiting the
differentiation capacities of adult stem cells. By
"reprogramming" adult stem cells so that they can
turn on the genes that allow versatility,
scientists hope to cause them to revert to a more
flexible state. It is even possible that scientists
could one day "reprogram" any cell, not only
stem cells. However, research in this area is in the
early stages and scientists may be many years
away from making an adult cell as versatile as an
embryonic stem cell.
Stem Cell Research Timeline [top]
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This Web page is based on
Understanding Stem Cells: An Overview of the Science and Issues from the National Academies.
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