NOVA scienceNOW: Stem Cells Breakthrough
Background
While current controversy centers on human embryonic stem cells, your students may be surprised to
learn there are stem cells in their bodies right now. From birth, all humans—infants, children, and adults—
house populations of undifferentiated stem cells in the tissues of their bodies. These so-called "adult" stem
cells (the name is something of a misnomer, as these cells are also present in infants and children) give
rise to new specialized cells, such as neurons, blood cells, and muscle cells, as the body grows and repairs
itself over time. Blood-forming stem cells in the bone marrow, for example, give rise to red blood cells,
white blood cells, and platelets.
Adult stem cell research is a rapidly expanding field filled with many important, as yet unanswered,
questions. What, for example, is the source of the stem cells found in adults? Are they leftover embryonic
stem cells that never differentiated? Where in the body are they manufactured? How plastic are they—that
is, how many different kinds of structures can they differentiate into? As you discuss stem cell science
with your students, remind them of the compelling questions remaining in this broad and emerging field.
To help students understand stem cells, it is useful to review the basics of fertilization and differentiation.
When a sperm cell fertilizes an egg cell, the resulting fertilized egg, or zygote, has the potential to divide
and differentiate into every single type of cell in the body.
The fertilized egg, then, is the ultimate stem cell, an unspecialized cell that divides repeatedly and, when
the right set of signals is received, differentiates into the specialized cells that make up the body's heart,
bones, skin, muscles, and other tissues and organs. Scientists sometimes call the fertilized
egg totipotent, meaning it has the potential to differentiate into any cell type in the body. The term
comes from the Latin roots totus, or "entire," and potens, "able."
Soon after fertilization, the egg cell begins to divide, and after about 4-5 days, the dividing cells take the
shape of a hollow ball called a blastocyst. In animal development, the blastocyst is one of the first stages
in the formation of an embryo. By the time the blastocyst forms, initial stages of differentiation are
already taking place—some cells form the outer wall of the sphere, while a cluster of cells called the inner
cell mass begins to assemble on one end inside the sphere. This cluster of inner cells eventually becomes
an embryo and then, as development proceeds, a fetus; the outer cells ultimately differentiate into the
placenta.
Inner mass cells, also called embryonic stem cells, have the ability to differentiate into almost any cell
in the human body. Embryonic stem cells retain this potential early in development, but approximately
two weeks after fertilization in humans, the cells begin to move, arranging themselves into three layers.
The outermost layer, the ectoderm, eventually becomes the skin and components of the nervous system.
The middle layer, ormesoderm, becomes the muscles, blood, bones, heart, and circulatory system, and
the inner layer, or endoderm, becomes the lungs, digestive tract, bladder, and glands such as the
pancreas and liver.
This differentiation process, called gastrulation, is an important step in development. Cells become
successively bound to a particular destiny as development proceeds; when the cells of the inner cell mass
migrate to the ectoderm, for example, they become committed to a pathway that will lead them to
differentiate into skin or nerve cells, but not blood cells. Later steps in differentiation will lead some
ectoderm cells to become skin cells, but not nerve cells, and so on. Differential gene expression—turning
different genes "on" or "off"—drives this process. As students will learn in the NOVA scienceNOW
segment Stem Cell Breakthrough, some scientists are trying to cause cells to revert to an earlier stage
in differentiation, or to coax them to follow different pathways, by manipulating their genes. In this way,
researchers hope to develop novel medical treatments, such as making new nerve cells to replace
damaged ones.
Scientists investigating human embryonic stem cells obtain these cells from the inner cell mass of
blastocysts at fertility clinics. The cells derived from these sources are obtained only with donor consent
and the understanding that the fertilized egg will be used strictly for research. Still, research on human
embryonic stem cells remains a hotly debated topic in the United States today. As of this writing, federal
funding for research on human embryonic stem cells is limited to the cell lines produced prior to August,
2001.
http://learn.genetics.utah.edu/content/tech/stemcells/ips/
STEM CELL QUICK REFERENCE
Are you confused about all the different types of stem cells? Read on to learn where different types of stem cells come
from, what their potential is for use in therapy, and why some types of stem cells are shrouded in controversy.
EMBRYONIC STEM CELLS
Embryonic stem (ES) cells are formed as a normal part of
embryonic development. They can be isolated from an
early embryo and grown in a dish.
Potential as therapy
ES cells have the potential to become any type of cell in
the body, making them a promising source of cells for
treating many diseases.
Special considerations
Without drugs that suppress the immune system, a
patient's immune system will recognize transplanted cells
as foreign and attack them.
Ethical considerations
When scientists isolate human embryonic stem (hES) cells
in the lab, they destroy an embryo. The ethical and legal
implications of this have made some relunctant to support
research involving hES cells.
SOMATIC STEM CELLS
Somatic stem cells (also called adult stem cells) exist
naturally in the body. They are important for growth,
healing, and replacing cells that are lost through daily
wear and tear.
Potential as therapy
Stem cells from the blood and bone marrow are
routinely used as a treatment for blood-related diseases.
However, under natural circumstances somatic stem
cells can become only a subset of related cell types.
Bone marrow stem cells, for example, differentiate
primarily into blood cells. This partial differentiation can
be an advantage when you want to produce blood cells;
but it is a disadvantage if you're interested in producing
an unrelated cell type.
Special considerations
Most types of somatic stem cells are present in low
abundance and are difficult to isolate and grow in culture.
Isolation of some types could cause considerable tissue or organ damage, as in the heart or brain. Somatic stem cells can
be transplanted from donor to patient, but without drugs that suppress the immune system, a patient's immune system will
recognize transplanted cells as foreign and attack them.
Ethical considerations
Therapy involving somatic stem cells is not controversial; however, it is subject to the same ethical considerations that
apply to all medical procedures.
INDUCED PLURIPOTENT STEM CELLS
Induced pluripotent stem (iPS) cells are created artificially
in the lab by "reprogramming" a patient's own cells. iPS
cells can be made from readily available cells including fat,
skin, and fibroblasts (cells that produce connective tissue).
Potential as therapy
Mouse iPS cells can become any cell in the body (or even
a whole mouse). Although more analysis is needed, the
same appears to be true for human iPS cells, making them
a promising source of cells for treating many diseases.
Importantly, since iPS cells can be made from a patient's
own cells, there is no danger that their immune system will
reject them.
Special considerations
iPS cells are much less expensive to create than ES cells
generated through therapeutic cloning (another type of
patient-specific stem cell; see below).
Ethical considerations
Therapy involving iPS cells is subject to the same ethical considerations that apply to all medical procedures.
THERAPEUTIC CLONING
Therapeutic cloning is a method for creating patientspecific embryonic stem (ES) cells.
Potential as therapy
Therapeutic cloning can, in theory, generate ES cells
with the potential to become any type of cell in the
body. In addition, since these cells are made from a
patient's own DNA, there is no danger of rejection by
the immune system.
Special considerations
Scientists have not been able to grow a cloned human
embryo to the blastocyst stage. In other animals, the
cloning process has been time consuming, inefficient,
and expensive.
Ethical considerations
Therapeutic cloning brings up considerable ethical
considerations. It involves creating a clone of a human
being and destroying the cloned embryo, and it
requires a human egg donor.
THE STORY OF IPS CELLS
Until fairly recently, differentiation was seen as final and irreversible. Once a
cell became specialized, it was referred to as "terminally differentiated;" it
was considered locked in and unable to become a different cell type.
However, in 2007, scientists were able to turn a differentiated cell back into
a stem cell with the potential to become any type of cell in the body.
The difference between a stem cell and a differentiated cell is reflected in
the cells' DNA. In a stem cell, the DNA is arranged loosely, with its genes
ready to spring into action. As signals enter the cell and differentiation
begins, genes that will not be needed are shut down, and genes that will be
required for a specialized function remain open and active.
Scientists also noticed that a small number of genes were active only in
stem cells, and not in differentiated cells. Scientists in Japan wanted to see if
introducing these genes back into differentiated cells could make them
behave more like stem cells.
By introducing a cocktail of 24 different genes, the scientists were able to convert differentiated cells into stem cells. They
gradually eliminated genes from the mixture, and in the end they were able to turn differentiated cells into stem cells by
activating just 4 genes. These genes appear to be remodeling the cells' DNA, unlocking the genes that were shut down
during differentiation.
Armed with the ability to reverse the differentiation process, scientists are exploring new ways to use stem cells in
research and medicine.