| Stem Cells: What Are They and What
Promise Do They Hold?
What is so special about stem cells? Why are they sometimes
considered controversial when their use potentially can help so
many people?
What is a Stem Cell?
All mammals begin as two cells --
sperm and egg -- that combine into a single cell. This single
cell will divide exponentially into specialized cells making up
various organs and systems -- all the tissues of a new organism.
Simply put, a stem cell is an
immature cell that can become a different cell, or perhaps
become one of many different cells. Most stem cells also can
renew themselves -- divide -- indefinitely. These two
characteristics are what present a new pathway to repairing
damage to the human body caused by trauma, degeneration and
disease.
Types of Stem Cells
Thus far research has revealed
two basic classes of stem cells: embryonic and adult.
As one might think, embryonic stem cells are found in embryos or
in fetal tissue. These stem cells are either totipotent or
pluripotent. Totipotent
stem cells have the potential become any cell in the body from
the total range of possibilities (brain, heart, liver, skin,
etc.). Pluripotent
stem cells can develop into almost all of the more than 200
known cell types.
Adult
stem cells by contrast are unspecialized cells that occur in
already specialized tissue. These stem cells are found in
mammals that are more mature than the fetal stage. Adult stem
cells are called multipotent
because they can become one kind of a certain type of cell, but
not any type of cell. An example of a multipotent stem
cell is a blood stem cell that could become a white blood cell,
a red blood cell, or a platelet; it could not, however, become a
nerve cell. Adult stem cells can replicate for the life of an
organism, but they cannot replicate indefinitely like totipotent
and pluripotent stem cells can.
According to the National
Institutes of Health''s primer on stem cells (http://www.nih.gov/news/stemcell/primer.htm),
the development of totipotent, pluripotent and multipotent stem
cells can be illustrated by a review of normal human
development. The single cell created from a fertilized egg has
the potential to form an entire, or total, organism. This single
cell is therefore totipotent. In the first hours after
fertilization, this single cell divides into two identical
totipotent cells, either of which, if placed into a woman''s
uterus, could develop into a fetus. Approximately four days
after fertilization and after several cycles of cell division,
these totipotent cells begin to specialize, forming a hollow
sphere of cells called a
blastocyst. An outer layer of cells and a cluster of
cells -- called the inner cell mass -- inside the hollow sphere
comprise the blastocyst. The outer layer of cells will form the
placenta and other supporting tissues needed for development in
the uterus. The cells in the inner mass will form all the cells
of the organism, but they cannot themselves form an organism
because they cannot form the placenta and supporting tissues
that would enable an organism to develop. The inner mass cells
are pluripotent. These pluripotent cells become
specialized into multipotent stem cells at a later stage
of development. Multipotent stem cells thus far have been found
in several areas of the body, including in the hippocampus area
of the brain and in the blood.
Issues in Stem Cell Research
With a basic understanding of
what stem cells are, what different kinds of stem cells can do
and where they can be found, some of the ethical concerns in
pursuing stem cell research in humans become clearer. It is
important to note that, while scientists have been studying
human development for years, it is only in 1998 that they were
able to isolate pluripotent stem cells from human embryos and
grow them in the laboratory. Given the properties of pluripotent
cells -- they are able to replicate indefinitely in the
laboratory to develop into almost all types of cells in the body
-- the 1998 findings were momentous. But even though pluripotent
cells primarily are found in the blastocyst''s inner mass (they
also are found in fetal tissue destined to develop into sexual
organs), which cannot alone develop into an organism, an embryo
is destroyed when the pluripotent cells are obtained.
In August 2001 the United States
government approved federal funding for research on the 60-plus
stem cell lines that at that time were already created through
private research. To qualify for research through federal
funding, these stem cell lines must have been created: with the
informed consent of the donors; from excess embryos created for
reproductive purposes only; and without financial inducements to
the donors. Federal funds cannot be used for: derivation or use
of stem cell lines derived from newly destroyed embryos; the
creation of any human embryos for research purposes; or the
cloning of human embryos.
Research on the complexities of
stem cells, as well as the applications of the research for
humans, continues at a great pace on all types of stem cells.
While pluripotent stem cells still seem to offer the most
promise for human therapies, research on adult stem cells has
not been dismissed. However, while it would seem to be easier to
obtain adult stem cells and avoid some of the ethical issues
associated with embryonic stem cells, there are some issues to
resolve here, as well. Adult stem cells have not yet been
identified in every part of the body; they are multipotent, not
pluripotent; and they are difficult to identify, isolate, and
purify. A notable drawback to utilizing adult stem cells in
therapies is that there are insufficient numbers of cells
available for transplantation because in a culture dish they are
unable to replicate over extended periods of time. Researchers
also have been unsuccessful in directing these cells to become
functional as specialized cells. They have had some success with
adult stem cells from the bone marrow, umbilical cord blood, and
in the brain, particularly in the hippocampus region. Also,
recent research has introduced the property of
plasticity in adult
stem cells. That is, some adult stem cells have been shown to be
capable of generating the specialized cell type of another
tissue. A reported example of plasticity involved adult stem
cells from bone marrow that generated cells resembling
neurons -- the functional
units of the nervous system found in the brain and spinal cord.
The recent advances in our
ability to manipulate adult and embryonic stem cells have opened
a whole new spectrum of potential therapies for many disorders
of the human body. However, to date, neither adult stem cells
nor embryonic stem cells have been used to treat neurological
disorders in humans. But progenitor cells have shown some
promise in this area.
Progenitor Cells
A progenitor (or precursor) cell,
found in both adult and fetal tissues, is a partially
specialized cell that, when it divides, can form more progenitor
cells or two specialized cells. (In contrast, when a stem cell
divides, one of the two new cells can replicate itself again.)
Progenitor cells can replace cells that are damaged in the
nervous system (where they are called neural progenitor cells)
and elsewhere.
Many early studies reported
successfully obtaining progenitor cells from various regions of
the brain (primarily the subventricular zone), growing them in
the laboratory, and transforming them into functional neurons.
One challenge is to better identify these cells and to
understand their mechanisms of growth and specialization from
embryonic stem cells. Both fetal and adult neural progenitor
cells show much promise in brain repair. In recent experiments
they have been shown to survive and specialize in the diseased
animal brain after injury. It appears that the host brain
receiving the cells may influence how the new cells behave. The
potential in this area of research is immense.
Neuronal cells derived from a
cancer cell line (teratocarcinoma) have been well studied and
now tested in humans. Research in normal animals and in animals
after injury showed that the cells behaved well and were
associated with some recovery of neurological deficits. The
initial human trials in patients with small strokes that have
caused paralysis are continuing.
Stem Cell Applications for
Neurosurgery
Modern restorative neurosurgery
began more than 25 years ago when neurosurgeons and
neurobiologists envisioned the possibility of replacing
degenerating neurons in patients who had diseases like
Parkinson''s and Huntington''s. At the time it was believed that
neurons could not regenerate, a dogma that was disproved in the
1990s. Therefore, early clinical trials were based first on a
direct approach targeting the replacement of missing specific
brain chemicals (neurotransmitters) rather than regenerating the
damaged neuronal circuitry. More recently, with the advent of
treatment strategies developed from experimental work with stem
and progenitor cells, there is hope that the final goal of
reconstructing neuronal pathways may be achieved. The goals of
this field can be summarized as replacement, release,
and regeneration. That is, dead neurons have to be
replaced, the grafts have to be able to release
neurotransmitters, and circuits have to be rebuilt. Of course,
these goals can be fulfilled only if scientists'' understanding
of the mechanisms of disease keeps up with the pace of
development of new bioengineering strategies.
Currently grafts from fetal
tissue, tumor lines and stem cells have been transplanted.
Successes in animal models have led to transplant trials in the
human population to treat Parkinson''s disease, Huntington''s
disease, spinal cord injury and stroke. As research in animal
models progresses, transplant trials may be initiated for the
treatment of multiple sclerosis, traumatic brain injury,
cerebral palsy, ALS, Alzheimer''s disease, and other disorders.
Copyright© 1998-2000; American Association of Neurological
Surgeons /
Congress of Neurological Surgeons |
