From Harvard Health Publications
CORRECTED HANDOUT
March 23 Longwood Seminar at Harvard Medical School
Stem Cells:
Hope Beyond the Hype
Why Are People Excited About The Potential Of Stem Cells?
Background To Understanding Stem Cells
What Are Stem Cells?
Are Stem Cells Used In Treating Human Diseases?
Making Your Own Stem Cells Through Nuclear Transfer
Why Are People Excited About The Potential Of Stem Cells?
Most diseases are caused by the death of healthy cells in a particular organ.
For example, diabetes is caused by the death of insulin-producing cells in
the pancreas (an organ that lies beneath the stomach); Parkinson’s disease
is caused by the death of brain cells that produce a chemical called dopamine;
and heart attacks cause the death of heart-muscle cells. Almost all the organs
in our bodies cannot, on their own, replace the cells that die (the liver is
an exception). Nor have medicines been discovered that prompt our bodies to
replace dead cells.
Stem cells have the capability to replace cells that have died, in different
organs. In mice, stem cells have in fact replaced dead cells, and cured the
mice of particular diseases (including heart-muscle damage). That is the main
reason
that there is such excitement about using stem cells for what is called “cell
therapy.”
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Background To Understanding Stem Cells
Before explaining what a stem cell is, we need to describe what cells and organs
are.
Cells — Every animal and human being is composed of cells. Each human
being consists of trillions of cells.
Organs — Cells are grouped together into organs — for example, the
eye, the brain, the heart, the pancreas. Within each organ are groups of different
types of cells. These different types of cells support each other and even “talk” to
each other using chemical signals.
The three miracles of development
The first miracle of development is that all of those trillions of cells came
originally from just one cell: the fertilized egg. The second miracle is that
all of these cells are so different from one another, each specialized for
a particular purpose. Certain cells in the back of our eyes detect light, allowing
us to see. Certain cells lining our stomach make acid that helps to digest
food.
Certain cells in the pancreas make insulin, which drives a source of energy
(sugar) inside our cells. These different types of cells, which live in different
organs,
are called specialized cells.
The third miracle is that all of the specialized cells are formed in the right
place (the light-sensing cells in the eye, the acid-producing cells in the
stomach), and in the right number: not too many and not too few. First inside
the mother’s
womb, and then outside, some miraculous process in each of us has directed
one cell to both multiply and to change into very different cells, in a highly
controlled
way.
How genes control our development
What controls the process of growth and development? Inside every human cell
is a set of about 30,000 genes — the same 30,000 genes in each cell.
Genes only work when they are turned on. What makes one specialized cell different
from another type of specialized cell is that different genes are turned on
and
off in each type of cell. For example, different genes are turned on and off
in the light-sensing cells of the eye than in the acid-producing cells of the
stomach.
But what controls the turning on and off of different genes? Chemical signals
in the immediate environment — chemicals produced by the cells next door — activate
or inactivate certain genes. Recently, scientists have begun to identify which
genes are turned on or off in a particular type of cell, and what the chemical
signals are that influence these genes.
One final concept is important. Once a cell has become specialized, it cannot
make copies of itself, and it generally cannot turn into any other type of
cell. With a few exceptions, once a cell has become specialized, it will exist
unchanged
until it dies.
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What Are Stem Cells?
In addition to the trillions of specialized cells, we also carry within us
a small number of cells called stem cells. Stem cells can reproduce themselves,
and they can go on to produce specialized cells — if they are coaxed
to do so by certain chemical signals.
There are several types of stem cells
Embryonic stem cells are found in an early stage of the embryo.
These cells — discovered
in mice 20 years ago, and in humans about six years ago — can reproduce
themselves, producing more embryonic stem cells, or they can turn into many
and perhaps all specialized cell types.
Umbilical-cord stem cells are present
in
the umbilical-cord blood, which is removed at the time of birth. They are currently
used in treatment of human blood cancers and related conditions, as explained
below.
Adult (or somatic) stem cells are found in certain organs,
such as the bone marrow, brain, muscles and skin. These cells also can reproduce
themselves,
and they can turn into different specialized cells of the organ where they
are found. For example, brain stem cells can form into neurons — the
cells responsible for the main activities of the brain, such as thinking, emotion,
vision, hearing, and directing body movement. Blood stem cells, for example,
can produce oxygen-carrying red blood cells, all the different types of white
blood cells, and the cells that form blood clotting cell fragments called platelets.
There is some evidence that adult stem cells may be able to turn into some
types of specialized cells found in organs other than their own. For example,
bone-marrow
cells may be able to turn into heart-muscle cells. There is considerable controversy
as to how capable adult stem cells are in this regard. However, there is no
doubt that embryonic stem cells are capable of turning into many more types
of specialized
cells than are adult stem cells.
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Are Stem Cells Used In Treating Human Diseases?
For many years, doctors have used adult stem cells successfully in treating
human disease, through bone-marrow transplantation. Bone-marrow transplantation
is
used most often in the treatment of cancers, particularly cancers that require
chemotherapy.
When chemotherapy is given to kill cancer cells, it also kills many bone-marrow
cells. Very high doses of chemotherapy kill more cancer cells but also kill
more bone-marrow cells. Without bone-marrow stem cells, a person would be unable
to
make the blood cells that are essential for life.
In autologous bone-marrow transplantation, patients donate their own cells
prior to receiving chemotherapy. The cells from the bone marrow are removed
through
a needle. The removed cells include adult stem cells, the kind that make all
of the blood cells. Those adult stem cells are put in laboratory dishes that
are filled with nutrients, where they multiply.
Then high-dose chemotherapy is given — a dose that will kill all the bone-marrow
cells in the body but that also, hopefully, will kill all the cancer cells. Then
your own bone-marrow cells that have been multiplying in the laboratory are placed
back into your body. When the procedure works, the bone-marrow stem cells begin
making new blood cells — and the cancer is cured.
Although using bone-marrow transplantation is a common example of using a particular
type of adult stem cell — bone-marrow blood-forming stem cells — to
replace dead cells, it currently is the only such common example. If you need
to replace cells in your brain, heart, liver, kidneys — indeed, all organs
other than the blood — there is currently no stem cell therapy.
In recent years, umbilical-cord stem cells also have been used in place of
bone-marrow adult stem cells, for transplantation. They have some advantages
compared to
bone-marrow cells: they are at least as likely to successfully grow into healthy
adult blood cells, and are less likely to have certain major side effects.
Umbilical-cord stem cells can be easily extracted at the time of a baby’s
birth, and frozen away for years. Theoretically, should that baby need a transplantation
for blood cancer or other condition later in life, the frozen umbilical-cord
cells would be ideal, because they could be transplanted without fear of rejection
by the immune system. Some companies offer parents the service of collecting
and freezing a baby’s cord blood. While there may be cases where that makes
sense — such as a baby born to a family that seems to have a high rate
of blood cancer — most experts do not think there are currently many circumstances
under which it would be appropriate to collect and freeze a baby’s cord
stem cells at the time of birth.
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Making Your Own Stem Cells Through Nuclear Transfer
Suppose you had a failing organ, and wanted to use embryonic stem cells for
cell therapy. The embryonic stem cells would have to be your own, because embryonic
stem cells from another human being would be recognized as foreign by your
immune
system and rejected.
But how could you use your own embryonic stem cells, since you were an embryo
a long time ago, and you can’t turn back the clock? Scientists are working
on a technique called somatic cell nuclear transfer (SCNT) that
could do the trick.
In normal development, a sperm fertilizes an egg. The sperm carries half of
the father’s genes and the egg carries half of the mother’s genes in
the nucleus of the egg. The fertilized cell (called a zygote) has the full number
of genes. The zygote begins to divide, and after several days an early stage
of the embryo — the blastocyst — is created. The blastocyst lodges
in the lining of the mother’s uterus, and begins to grow into a baby.
Using Somatic Cell Nuclear Transfer For Creating Stem Cells Is Fundamentally
Different From Using It For Reproductive Cloning
SCNT involves removing the nucleus of a donor's unfertilized egg and
replacing it with the nucleus of an adult cell, such as a skin, heart or nerve
cell.
No sperm is used in the procedure. The goal is to create embryonic stem cells,
and the cell, with its new nucleus is placed in a lab dish and stimulated
to begin dividing. After five or six days, it develops into a hollow cellular
ball from which researchers can extract embryonic stem cells.
The first human embryonic stem cells created through SCNT were developed by scientists in South Korea in February 2004. With adequate support, other scientists using and refining this method will be able to produce more human stem cell lines.