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Stem cells are cells that divide to form
 | one daughter that goes on to differentiate, and |
| one daughter that retains its stem-cell properties. |
Several adjectives are used to describe the developmental potential
of stem cells; that is, the number of different kinds of differentiated
cell that they can become.
- Totipotent cells. In mammals, totipotent cells have the
potential to become
The only totipotent cells are the fertilized egg and the
first 4 or so cells produced by its
cleavage (as shown by the ability of mammals to produce identical
twins, triplets, etc.).
In mammals, the expression totipotent
stem cells is a
misnomer: these cells fail to meet the second criterion — they cannot
make more of themselves.
Pluripotent stem cells. These are
true stem cells, with the potential to make any differentiated cell in
the body, but cannot contribute to making the extraembryonic membranes
(which are derived from the trophoblast).
Three types of pluripotent stem cells have been found
 | Embryonic Stem (ES) Cells. These can be isolated from the
inner cell mass (ICM) of the blastocyst — the stage of
embryonic development when implantation occurs. For humans, excess
embryos produced during
in vitro fertilization (IVF) procedures are used. Harvesting ES
cells from human blastocysts is controversial because it destroys
the embryo, which could have been implanted to produce another baby
(but often was simply going to be discarded). |
| Embryonic Germ (EG) Cells. These can be isolated from the
precursor to the gonads in aborted fetuses. |
| Embryonic Carcinoma (EC) Cells. These can be isolated
from teratocarcinomas, a tumor that occasionally occurs in a gonad
of a fetus. Unlike the other two, they are usually
aneuploid. |
All three of these types of pluripotent stem cells
| can only be isolated from embryonic or fetal tissue; |
| can be grown in culture, but only with special methods to
prevent them from differentiating. |
Multipotent stem cells. These are
true stem cells but can only differentiate into a limited number of
types. For example, the bone marrow contains multipotent stem cells
that give rise to all the cells of the blood but not to other types of
cells. [Discussion]
Multipotent stem cells are found in adult animals; perhaps most
organs in the body (e.g., brain, liver) contain them where they can
replace dead or damaged cells. These adult stem cells may also be the
cells that — when one accumulates sufficient mutations — produce a
clone of
cancer cells.
Many medical problems arise from damage to differentiated cells.
Examples:
| Insulin-dependent diabetes mellitus (IDDM) where the
beta cells of the pancreas
have been destroyed by an
autoimmune attack; |
| Parkinson's disease; where
dopamine-secreting cells of the brain have been destroyed; |
| spinal cord injuries leading to paralysis of the skeletal muscles;
[View]
|
| ischemic stroke where a blood clot in the brain has caused neurons
to die from oxygen starvation; |
|
multiple sclerosis
with its loss of myelin sheaths around
axons. |
| blindness caused by damage to the
cornea. |
The great developmental potential of stem cells has created intense
research into enlisting them to aid in replacing the lost cells of such
disorders.
While some success has been achieved with laboratory animals, not
much has yet been achieved with humans.
One exception: culturing human epithelial stem cells and using their
differentiated progeny to replace a damaged cornea. This works best when
the stem cells are from the patient (e.g. from the other eye). Corneal
cells from another person (an
allograft) are always at risk of rejection by the recipient's immune
system.
So one major problem that must be solved before human stem cell
therapy becomes a reality is the threat of rejection of the transplanted
cells by the host's immune system (if the stem cells are allografts;
that is, come from a genetically-different individual).
One way to avoid the problem of rejection is to use stem cells that
are genetically identical to the host.
This is already possible in the rare situations when the patient has
healthy stem cells in an undamaged part of the body (like the stem cells
being used to replace damaged corneas).
But even where no "autologous" stems cells are available, there may
be a solution: using
somatic-cell nuclear
transplantation (but with no goal of
attempting to implant the resulting blastocyst in a uterus).
In this technique,
| A human egg has its own nucleus removed and replaced by |
| a nucleus taken from a somatic (e.g., skin) cell of the patient.
|
| The now-diploid egg is allowed to develop in culture to the
blastocyst stage when |
| embryonic stem cells can be harvested and grown up in culture.
| This much has now been achieved with humans -
Link |
|
| When they have acquired the desired properties, they can be
implanted in the patient with no fear of rejection. |
While an exciting prospect, there are still problems with the method
that must be solved.
| Imprinted Genes.
Sperm and eggs each contain certain genes that carry an "imprint"
identifying them later in the fertilized egg as being derived from the
father or mother respectively.
Creating an egg with a nucleus taken from an adult cell may not
allow a proper pattern of imprinting to be established.
When the diploid adult nucleus is inserted into the enucleated egg
(at least those of sheep and mice), the new nucleus becomes
"reprogrammed". What reprogramming actually means still must be
learned, but perhaps it involves the proper
methylation and
demethylation of imprinted genes. For example, the
inactive X chromosome in adult female cells must be reactivated in
the egg, and this actually seems to happen. |
| Aneuploidy.
In primates (in contrast to sheep, cattle, and mice), the process
of removing the resident nucleus causes molecules associated with the
centrosome to be lost as well. Although injecting a donor nucleus
allows mitosis to begin, spindle formation may be disrupted, and the
resulting cells fail to get the correct complement of chromosomes (aneuploidy).
|
| Somatic Mutations. This procedure also raises the spectre
of amplifying the effect(s) of somatic mutations. [Link
to discussion]
In other words, mutations that might be well-tolerated in a single
somatic cell of the adult (used to provide the nucleus) might well
turn out to be quite harmful when they become replicated in a clone of
cells injected later into the patient. |
| Political Controversy.
The goal of this procedure (which is often called "therapeutic
cloning" even though no new individual is produced) is to culture a
blastocyst that can serve as a source of ES cells.
But that same blastocyst could theoretically be implanted in a
human uterus and develop into a baby that was genetically identical to
the donor of the nucleus. In this way, a human would be cloned.
And in fact, Dolly and other animals are now routinely cloned this
way.
Link to a description.
The spectre of this is so abhorrent to many that they would like to
see the procedure banned despite its promise for helping humans.
In fact, many are so strongly opposed to using human blastocysts —
even when produced by nuclear transfer — that they would like to limit
stem cell research to adult stem cells
(even though these are only multipotent).
One possible solution: It now appears that ES cells can be derived
from a single cell removed from a human
morula — an earlier stage in embryonic development.
Removing a single cell from the morula does not destroy it [link
to evidence]. |
| In the 12 March 2004 issue of Science, a group of Korean
scientists (such government-funded work is currently forbidden in
the US) reported that they had created human ES cells from
blastocysts produced following somatic cell nuclear transfer (SCNT).
In each case, the donor nucleus came from the same woman who
provided the enucleated egg.
When injected into
SCID mice, these cells formed teratomas; tumors containing a mix
of differentiated human cell types, including cells characteristic
of
ectoderm, mesoderm, and
endoderm. |
|
