A reserve cell with the capacity to grow and multiply to replace
dead or damaged adult cells. Some, but not all, organs and tissues in the body
have a supply of stem cells - skin
an example: skin wounds are repaired by skin stem cells, similarly, liver damage
is repaired by liver stem cells. Reserve stem cells do not, however,
for many vital tissues, including: heart, spinal cord, brain and pancreas. Scientists
are developing new sources of stem cells for these tissues.
Key Term: "Pluripotent" (adjective):
The capacity to become any cell in the body.
Pluripotent stem cells show the most promise for use in stem cell therapies.
Embryonic stem cells are pluripotent, adult stem cells are not.
How many kinds of stem cells are there?
The answer to this question is not known with certainty. Researchers
in the field divide stem cells into four broad catagories:
adult stem cells,
fetal stem cells,
embryonic stem cells, and
more recently(2007), induced stem cells.
These catagories refer to the source
of the cells, but do not describe their nature.
A new type of stem cell, nuclear transplant
stem cells ("ovasomes"), takes advantage of new methods to create stem cells.
Some of the methods are the same as those used for cloning animals, and thus,
this new methodology has been highly controversial.
Another new type of stem cell, parthenote stem
cells from "activated eggs", takes advantage of new methods to
stimulate unfertilized eggs to divide.
This new catagory
debate because it is less common and less well understood. It is becoming
however, that parthenote stem cells may have important therapeutic potential.
Types of Pluripotent Stem Cells
1) Embryonic stem cells from fertilized eggs are good models for research, but they have ethical issues, and will have tissue rejection problems (similar to bone marrow and kidney transplants).
2) Parthenote stem cells (derived from unfertilized eggs, "activated eggs") may be as pluripotent as embryonic stem cells, and have been the focus of BSCRF scientists for several years. Studies using monkey parthenote stem cells to treat Parkinson’s disease have been very promising.
Parthenotes do not have the potential tissue rejection problems faced by stem cells derived from fertilized eggs.
Unlike adult stem cells, parthenotes can potentially become any cell in the body.
Less controversial than stem cells
that are derived from fertilized eggs.
3) Induced Pluripotent stem cells (derived by adding proteins that reprogram adults cells, reverting them to their embryonic state) "These new cells are expected to live for a very long time while retaining the ability to form all of the different tissues found in a human body." Ian Wilmut, Time, April '08
Adult stem cells are the reserve supply of cells that can
multiply when needed for repair of adult organs and tissues. Skin
an example: skin wounds are repaired by skin stem cells, similarly, liver damage
is repaired by liver stem cells.
Adult stem cells
start out as embryonic stem cells, then become fetal stem cells, and mature
into adult stem cells. For example, if it takes 20 maturation steps for
an embryonic stem cell to turn into a mature skin cell, skin stem cells are
at step 15; they are not quite mature skin cells, but they cannot back-up
to become another cell type, such as a heart muscle cell.
Do all adult tissues and organs have stem cells?
This is not known for certain and is
an active area of research. It has long been thought that nerves, such as the spinal cord and brain, heart
and kidney are examples of organs that do not contain a reservoir of stem cells.
It is possible, however, that these organs and tissues do have a small reservoir
of stem cells that may be encouraged to multiply if the right conditions were
known. Whether or not sufficient numbers can be produced to cure such problems
as Parkinson's Disease and Heart Failure is not known.
The developing organs and tissues in a fetus contain a relatively
large supply of stem cells because they are needed for growth and maturation.
The difference between embryonic stem cells and fetal stem cells is the fetal
stem cells have matured part of the way to mature cells. For example, if it
takes 20 maturation steps for an embryonic stem cell to turn into a mature
skin cell, fetal skin cells are at step 10; they are not as mature as adult
skin stem cells, but they are past the stage of becoming committed to the liver.
Can fetal stem cells repair adult organs and tissues?
Possibly. There are currently several problems with the therapeutic
use of fetal stem cells.
First, fetal tissue research is highly controversial. There
are significant moral and ethical issues with the use of fetal tissues for research
purposes. Second, the numbers of stem cells in fetal tissues may not be sufficient
for the therapeutic needs of adults. Thus, methods need to be developed to greatly
expand the supply of fetal stem cells if they are to be therapeutically useful.
Third, tissue rejection problems similar to those encountered in kidney and
heart transplants may limit the usefulness of fetal stem cells.
Cells in the umbilical cord are "multipotent" and
can give rise to all the cells in normal bone marrow. Scientists are working
to discover if cord blood stem cells can multiply and become other types of
adult stem cells. For this reason many new parents have their new baby's umbilical
cord blood cryopreserved for potential future use.
Eggs fertilized by sperm begin to divide into multiple
cells, but do not begin to form organs and tissues for at least two weeks.
During this early developmental period, the cells that will ultimately
give rise to the developing fetus can be encouraged to grow indefinitely
in the laboratory as stem cells that are not committed to any
particular tissue. With the right mixture of hormones and growth factors,
embryonic stem cells can be encouraged to become many types of adult
cells such as: nerves, heart muscle, and insulin-producing cells. Animal
models, such as mice, have been used to demonstrate the important therapeutic
potential of these cells in treating the symptoms of such diseases as
Parkinson's Disease and Diabetes.
There are two main problems with the use of embryonic
stem cells for therapeutic purposes. First is the moral and ethical debate
that surrounds the use of a fertilized human egg for research and therapy.
Second is the potential for tissue rejection (similar to the rejection
in a liver or blood transplant) that could limit the therapeutic usefulness
stem cells. For this reason the Bedford Stem Cell Research Foundation is
focused on developing stem cells from unfertilized eggs.
Schematic of the development of
embryonic stem cells for research.
An egg ready to be fertilized extrudes one half
its chromosomes (top left) to make room for the sperm's chromosomes.
The sperm enters the egg, activates it, and the egg begins to divide into
(bottom left) and smaller cells (top right, a "morula").
At approximately 100 cells, the cells on the outside form a sealed
layer that surrounds
a fluid-filled cavity with a group of cells inside (Blastocyst).
The inside cells (small red) can be removed to a petri dish (bottom
right) and will
continue to divide into embryonic stem cells.
In the course of trying to understand how cells became
committed to each tissue and organ in the body, scientists discovered
that if the chromosomes were removed from an egg, and replaced with the
chromosomes (in the nucleus) of an adult cell, it was possible to stimulate
the egg to begin to divide into multiple cells just as if it had been
fertilized with sperm. Thus, nuclear transplantation refers to the process
of replacing egg chromosomes with the chromosomes of another cell, usually
a cell that has been growing in the laboratory. This research success
made it possible to try to clone adult animals. It is important to note
that the success rate in cloning animals is very low, fewer than 1% of
eggs that undergo nuclear transplantation, but the success rate in stimulating
the transplanted egg into dividing into multiple cells is high. Thus,
such transplanted eggs may be ideal candidates for stem cells, but not
for producing clones.
Schematic of the development of nuclear transplant stem
egg ready to be fertilized (top middle) is stabilized on a microscope
state and its chromosomes removed with a fine glass needle. The
chromosomes in an adult
somatic cell (upper left) are transferred into the egg, and the egg is then activated,
by chemicals or a small electrical jolt. The activated, nuclear transplant egg
divides into smaller and smaller cells, then forms a blastocyst that looks very
much like the blastocyst from a fertilized egg. The inside cells (small red)
can be removed to a petri dish (bottom right) and will continue to divide into
nuclear transplant stem cells (ovasomes). (Click on image
It has been known for many years that human eggs occasionally
undergo spontaneous cell divisions. These dividing eggs lead to dermoid
cysts and to benign tumors known as teratomas, that contain several cell
types including skin and hair. If eggs could be routinely stimulated
to undergo cell division in the laboratory, this could be an especially
valuable source of stem cells that could bypass the moral, ethical, and
some of the tissue rejection problems associated with fetal and embryonic
stem cells, particularly for the woman donating the egg. For example,
a woman with diabetes or spinal cord injury, could donate her own eggs
for her own stem cells.
Update - December 19, 2007: International Stem Cell Corporation International Stem Cell Corporation recently announced that scientific team, led by Chief Scientist, Dr. Elena Revazova, has created a new class of human stem cell lines that do not involve the use of fertilized eggs and may enable hundreds of millions of people of different sex, ages and racial groups to benefit from cell based therapy with cells that will not be rejected by the patients own immune system after transplanting. The article was published in the on line edition of the well known peer-review publication, Cloning and Stem Cells on December 19, 2007 [More on iTunes]
Schematic of Parthenote stem cells.
An egg ready to be fertilized (top left) is activated by chemicals or a small
electrical jolt. The activated egg divides into smaller (bottom left) and smaller
(top right, a morula) cells. At approximately 100 cells, the cells on the outside
form a sealed layer that surrounds a fluid-filled cavity with a group of cells
inside (Blastocyst). The inside cells (small red) can be removed to a petri
dish (bottom right) and will continue to divide into parthenote stem cells.
More References About Induced Pluripotent Stem Cells
Original Publication from Cell: Induction of Pluripotent Stem Cells
from Adult Human Fibroblasts
by Defined Factors (pdf)
Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda,
and Shinya Yamanaka
DOI 10.1016/j.cell.2007.11.019 Excerpt: "SUMMARY:
Successful reprogramming of differentiated human
somatic cells into a pluripotent state would
allow creation of patient- and disease-specific
stem cells. We previously reported generation
of induced pluripotent stem (iPS) cells, capable
of germline transmission, from mouse somatic
cells by transduction of four defined transcription
factors. Here, we demonstrate the
generation of iPS cells from adult human dermal
fibroblasts with the same four factors: Oct3/4,
Sox2, Klf4, and c-Myc. Human iPS cells were
similar to human embryonic stem (ES) cells in
morphology, proliferation, surface antigens,
gene expression, epigenetic status of pluripotent
cell-specific genes, and telomerase activity.
Furthermore, these cells could differentiate
into cell types of the three germ layers in vitro
and in teratomas. These findings demonstrate
that iPS cells can be generated from adult
Wikipedia: Induced pluripotent stem cell Excerpt: "Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan in 2006. Yamanaka had identified genes that are particularly active in embryonic stem cells, and used retroviruses to transfect mouse fibroblasts with a selection of those genes. Eventually, four key pluripotency genes essential for the production of pluripotent stem cells were isolated; Oct-3/4, SOX2, c-Myc, and Klf4. Cells were isolated by antibiotic selection for Fbx15+ cells. However, this iPS line showed DNA methylation errors compared to original patterns in ESC lines and failed to produce viable chimeras if injected into developing embryos."
Article: A Breakthrough on Stem Cells
published in Time,
by Alice Nov 20, 2007 Excerpt: "In the journal Cell, Shinya Yamanaka of Kyoto University reports success in turning back the clock on cheek cells from a middle-aged woman, while James Thomson of University of Wisconsin, the first to isolate human embryonic stem cells, achieved the same feat with foreskin cells from a newborn baby."
Article: Stem cells: The magic brew
Nature 448, 260-262 (19 July 2007) | doi:10.1038/448260a; Published online 18 July 2007
Janet Rossant Excerpt: "Researchers have engineered embryonic stem-like cells from normal mouse skin cells. If this method can be translated to humans, patient-specific stem cells could be made without the use of donated eggs or embryos."
Press Release: Reprogrammed adult cells treat sickle-cell anemia in mice
CAMBRIDGE, Mass. (December 6, 2007), Whitehead Institute for Biomedical Research at MIT Excerpt:
"Mice with a human sickle-cell anemia disease trait have been treated successfully in a process that begins by directly reprogramming their own cells to an embryonic-stem-cell-like state, without the use of eggs. This is the first proof-of-principle of therapeutic application in mice of directly reprogrammed “induced pluripotent stem” (IPS) cells, which recently have been derived in mice as well as humans."
is a clone?
The term clone stems from the Greek word, klon, which
means twig. Since twigs can sometimes give rise to new trees, clone has
come to mean an adult individual that is genetically identical to another
individual. Scientists use the word clone to describe many routine laboratory
methods of generating multiple identical copies of something, including
bacteria, pieces of DNA, and cultured cells used for research. Identical
twins are naturally occurring clones of each other. A laboratory method
for producing cloned animals involves transplanting the nucleus of an
adult cell into an egg whose chromosomes have been removed. After artificially
stimulating the egg with the new nucleus into dividing into several cells,
it is placed in the uterus of an animal that thinks she is pregnant.
In a small percentage of cases, the "nuclear transplant embryo" can
give rise to a pregnancy. Unfortunately, for reasons not understood,
such cloned animals have a high incidence of serious health problems.
What are other sources of pluripotent stem cells?
The Foundation is focused on deriving stem cells from unfertilized eggs:
1) Those derived from eggs artificially activated without sperm
2) Those derived from eggs whose chromosomes have been removed and
replaced by chromosomes from another cell – "nuclear
transplant stem cells"
3) Possible new source: stem cells from adult testis
What is the best type of stem cell to use for therapy?
do not know yet.
Embryonic stem cells are good models for research, but will have tissue
rejection problems (similar to bone marrow and kidney transplants)
if used for therapies. Parthenote stem cells (derived from unfertilized eggs) may avoid
the tissue rejection problems of embryonic stem cells, but these
are not currently available for humans. Studies using monkey parthenote
cells to treat Parkinson’s disease have been promising. Nuclear transplant stem cells (also derived from unfertilized eggs)
may be the best for therapy, but no line of human transplant stem cells
exists. Induced pluripotent stem cells (derived by "reprogramming" protein in adult cells) "One day iPS cells may be used to replace cells damaged or lost in disease, but much remains to be learned before such therapy would be appropriate. As a step along the way, iPS cells from patients with an inherited disease will offer opportunities to study illnesses such as als and Parkinson's and psychological ailments, as scientists program the cells back to their embryonic state and watch them mature in the lab. In the process, they may pinpoint the breakdowns that lead to the disease. The precise mechanism that led to Yamanaka's and Thomson's achievement last year is not yet understood, but the potential of that achievement is; it is a potential that could be unlimited." - Ian Wilmut, Time, April 08
here for a graphic representation of Stem Cells.
Stem Cell Gold Rush
California's landmark stem cell research program made headlines nationally, but what's the latest story behind the science? QUEST investigates the potential for medical breakthroughs in the next decade and how the Bay Area is leading the way.
Stem Cell Gold Rush Educator Guide
Use this television story and educator guide to help your students learn exactly what stem cells are, their potential to help scientific research, and why their use has been controversial. 110b_stemcellgoldrush.pdf (406 KB)