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What are stem cells?
Stem cells comprise a number of different types of immature cells
that have 2 basic properties: they can divide many times and thereby make more,
similar, cells and they can mature into other types of cells. Stem cells, by
themselves, are not generally responsible for the function of any of our body’s
tissues or organs; it is the mature cells that come from stem cells that serve
this purpose. There are 3 basic types of stem cells - totipotent, pluripotent,
and multipotent. Each has a different capacity to divide and mature. The ultimate
stem cell, the totipotent stem cell, appears to have the capacity to divide
forever but, more importantly, it has the capacity to generate all other types
of stem cells and more mature cells derived from them and, by so doing, the
entire organism. The fertilized egg is such a cell and, if it is human, gives
rise to a human being if it is in the proper supportive environment (the womb).
These cells are created inside the woman after intercourse or they can be
created in a laboratory by combining eggs and sperm in a process called in
vitro fertilization (IVF). For totipotent stem cells created by IVF to mature
into a human being, however, they must be placed or implanted into a womb. Development
of a totipotent stem cell into a human being is a highly complex and highly
orchestrated series of events that takes place in the womb with all of the
cells of the body being produced in a highly organized manner and according to
a tightly constrained time-line. At present, our understanding of this process,
although we know quite a bit, is still very rudimentary and it is difficult to
recreate most of these processes in the laboratory (but see pluripotent stem
cells and multipotent stem cells).
What are pluripotent stem cells?
A pluripotent stem cell has most of the same properties of the
totipotent stem cell: it can divide seemingly forever and it can mature into
all the cells types that make up the body. What it cannot, is give rise to an
organism. That is, human pluripotent stem cells cannot give rise to a human
being. The reason for this is that even if they are implanted into the womb
they are incapable of attaching to it and because of this cannot create the
proper supportive environment to develop into an organism. Pluripotent stem
cells, however, can be grown in a dish in the laboratory. This allows
scientists to grow up very large numbers of these cells and, under proper
conditions, particular more mature cell types as well. At present, there are
two ways to produce pluripotent stem cells that can be grown in the laboratory.
First, they can be extracted from an IVF-derived embryo that has developed from
a totipotent stem cell (the fertilized egg) in a process that generally results
in the destruction of the embryo. These pluripotent stem cells are also known
as embryonic stem cells or embryo-derived pluripotent stem cells (ePSCs).
Pluripotent stem cells can also be created from more mature cells (such as skin
cells) in the laboratory by forcing or inducing these cells to become immature.
These induced pluripotent stem cells (iPSCs) have many of the same properties
of ePSCs but they have two major advantages: 1) their production does not
require the destruction of the embryo and 2) they can be derived from any
particular person such that the cells so derived match that person in two
important ways: a) immunologically, which is good for transplantation purposes
and b) genetically, which is good for modeling a genetic disease the person may
have.
What are multipotent stem cells?
A multipotent stem cell is a stem cell type that is more mature
than a totipotent stem cell or a pluripotent stem cell. As a result,
multipotent stem cells have a limited ability to divide – they divide a finite
number of times, and then stop. They also have a limited potential to mature –
they generate the mature cell types of only one organ or tissue type.
Multipotent stem cells, therefore, usually are named according to the type of
tissue that they mature into: hematopoietic stem cells give rise to the
components of the blood such as red blood cells, white blood cells, and
platelets while neural stem cells give rise to the components of the brain such
as neurons and glial cells. In addition to multipotent stem cells, there also
exist even more restricted stem cells that give rise to only one or two more
mature cells types of a given tissue. A glial-restricted neural stem cell, for
example, only gives rise to glial cells but not neurons. For the most part, for
all of the potential uses of stem cells, it is the multipotent stem cells or
one of its more mature derivatives that will ultimately be used, not the
pluripotent or totipotent stem cells because of tumor or ethical
considerations.
What can stem cells be used for?
The major reason that stem cells have generated the excitement
that they have, in both scientists and non-scientists alike, is that they have
several important uses that have never before been available:
1) They can
be used to increase our understanding of how the organism develops from the
totipotent stem cell to the embryo to the fetus to the baby and beyond. This
will allow us to understand and, perhaps, do something about all the many
things that can go wrong during development such as genetic diseases, effects
of intrauterine toxin exposure, effects of intrauterine infections, etc.
2) They can
be used as surrogate systems to develop new drugs or genetic therapies. Most
potential new drug therapies, for example, fail because they are initially
tested in animal tissues and in animals before they are tested in humans. Using
human tissues derived from pluripotent stem cells, rather than using animal
tissues, may greatly improve our efficiency at developing new, effective, and
safe drugs to be used to treat human disease.
3) They can
be used to model human diseases. Using pluripotent stem cells derived from
patients with genetic diseases will give us model systems that we can use in
the laboratory to both understand human diseases and, hopefully, to come up with
new treatments for them.
4) They can be
used to screen or develop drugs to treat particular people. Since we already
know that different people respond to drugs differently - some not at all, some
well, and some with very severe side-effects - we can use pluripotent stem
cells (and their derivatives) derived from individual people to help predict
which drugs they will best respond to with the least number of side-effects.
5) Finally,
these cells can be used for transplantation. Because iPSCs can divide so many
times and because they can mature into any cell type of the body, they have the
potential to be used to generate replacement tissues when disease or injury
damages our own tissues. Importantly, because iPSCs can be created from a
particular person, creating transplantable cells from these iPSCs means that
the person’s immune system may not reject those cells, the major problem with
tissue transplantation today. It is important to note, however, that
pluripotent stem cells themselves have a strong predilection to form tumors;
thus, it is not the pluripotent stem cells that are being considered for
transplantation but more mature cells derived from them as these more mature
cells do not form tumors.
What are neural stem cells and how they are being used?
Neural stem cells (also known as neural progenitors or neural
precursor cells) are a relatively undifferentiated population(s) of cells in
the central nervous system (the brain and spinal cord, CNS) that are thought to
give rise to the broad array of specialized cells of the CNS, including both neurons and glial cells. Long thought to be an exclusive component of the
developing CNS, these cells have been demonstrated to exist in adult animal, as
well as human, CNS. New
research showing that these cells can be isolated and cultured has, for
the first time, allowed consideration of using these cells as a transplantable
tissue for the repair of injury such as that sustained during traumatic brain
injury or stroke or the repair of pathological processes such as those seen in certain
genetic birth defects such as the lysosomal storage diseases. In addition, these
cells allow the detailed study of the mechanisms of neural differentiation and
the genetic and environmental signals that direct the specialization of the
cells into particular cell types. In fact, using neural stem cells derived
from induced pluripotent stem cells, researchers have begun to model human
neurological diseases, such as autism, in the laboratory. In animal studies,
promising research suggests that implantation of the cells into brain areas
that have been damaged leads to some recovery of function of those brain
areas. This aspect of research using neural precursors is only in its infancy
but some early clinical trials of human neural stem cells in the treatment of
genetic diseases have already started.
Other sources of information about stem cells:
National Institutes of Health
http://stemcells.nih.gov/info/basics/
International Society for Stem Cell Research
http://www.isscr.org/Stem_Cell_Basics/2687.htm
California Institute for Regenerative Medicine
http://www.cirm.ca.gov/Stem_Cell_Basics
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