What are adult stem cells?
An adult stem cell is
thought to be an undifferentiated cell, found among
differentiated cells in a tissue or organ that can renew
itself and can differentiate to yield some or all of the
major specialized cell types of the tissue or organ. The
primary roles of adult stem cells in a living organism are
to maintain and repair the tissue in which they are found.
Scientists also use the term somatic stem cell instead of
adult stem cell, where somatic refers to cells of the body
(not the germ cells, sperm or eggs). Unlike embryonic stem
cells, which are defined by their origin (cells from the
preimplantation-stage embryo), the origin of adult stem
cells in some mature tissues is still under investigation.
Research on adult stem
cells has generated a great deal of excitement. Scientists
have found adult stem cells in many more tissues than they
once thought possible. This finding has led researchers and
clinicians to ask whether adult stem cells could be used for
transplants. In fact, adult hematopoietic, or blood-forming,
stem cells from bone marrow have been used in transplants
for 40 years. Scientists now have evidence that stem cells
exist in the brain and the heart. If the differentiation of
adult stem cells can be controlled in the laboratory, these
cells may become the basis of transplantation-based
The history of
research on adult stem cells began about 50 years ago. In
the 1950s, researchers discovered that the bone marrow
contains at least two kinds of stem cells. One population,
called hematopoietic stem cells, forms all the types of
blood cells in the body. A second population, called bone
marrow stromal stem cells (also called mesenchymal stem
cells, or skeletal stem cells by some), were discovered a
few years later. These non-hematopoietic stem cells make up
a small proportion of the stromal cell population in the
bone marrow, and can generate bone, cartilage, fat, cells
that support the formation of blood, and fibrous connective
In the 1960s,
scientists who were studying rats discovered two regions of
the brain that contained dividing cells that ultimately
become nerve cells. Despite these reports, most scientists
believed that the adult brain could not generate new nerve
cells. It was not until the 1990s that scientists agreed
that the adult brain does contain stem cells that are able
to generate the brain's three major cell types¡Xastrocytes
and oligodendrocytes, which
are non-neuronal cells, and neurons,
or nerve cells.
A. Where are adult
stem cells found, and what do they normally do?
Adult stem cells have
been identified in many organs and tissues, including brain,
bone marrow, peripheral blood, blood vessels, skeletal
muscle, skin, teeth, heart, gut, liver, ovarian epithelium,
and testis. They are thought to reside in a specific area of
each tissue (called a "stem cell niche"). In many tissues,
current evidence suggests that some types of stem cells are
pericytes, cells that compose the outermost layer of small
blood vessels. Stem cells may remain quiescent
(non-dividing) for long periods of time until they are
activated by a normal need for more cells to maintain
tissues, or by disease or tissue injury.
Typically, there is a
very small number of stem cells in each tissue, and once
removed from the body, their capacity to divide is limited,
making generation of large quantities of stem cells
difficult. Scientists in many laboratories are trying to
find better ways to grow large quantities of adult stem
cells in cell culture and to
manipulate them to generate specific cell types so they can
be used to treat injury or disease. Some examples of
potential treatments include regenerating bone using cells
derived from bone marrow stroma, developing
insulin-producing cells for type 1 diabetes, and repairing
damaged heart muscle following a heart attack with cardiac
B. What tests are
used for identifying adult stem cells?
Scientists often use
one or more of the following methods to identify adult stem
cells: (1) label the cells in a living tissue with molecular
markers and then determine the specialized cell types they
generate; (2) remove the cells from a living animal, label
them in cell culture, and transplant them back into another
animal to determine whether the cells replace (or
"repopulate") their tissue of origin.
Importantly, it must
be demonstrated that a single adult stem cell can generate a
line of genetically identical cells that then gives rise to
all the appropriate differentiated cell types of the tissue.
To confirm experimentally that a putative adult stem cell is
indeed a stem cell, scientists tend to show either that the
cell can give rise to these genetically identical cells in
culture, and/or that a purified population of these
candidate stem cells can repopulate or reform the tissue
after transplant into an animal.
C. What is known
about adult stem cell differentiation?
As indicated above,
scientists have reported that adult stem cells occur in many
tissues and that they enter normal
differentiation pathways to form the specialized cell
types of the tissue in which they reside.
differentiation pathways of adult stem cells. In a
living animal, adult stem cells are available to divide,
when needed, and can give rise to mature cell types that
have characteristic shapes and specialized structures and
functions of a particular tissue. The following are examples
of differentiation pathways of adult stem cells (Figure
2) that have been
demonstrated in vitro or in vivo.
stem cells give rise to all the types of blood cells:
red blood cells, B lymphocytes, T lymphocytes, natural
killer cells, neutrophils, basophils, eosinophils,
monocytes, and macrophages.
Mesenchymal stem cells
give rise to a variety of cell types: bone cells (osteocytes),
cartilage cells (chondrocytes), fat cells (adipocytes),
and other kinds of connective tissue cells such as those
Neural stem cells in the
brain give rise to its three major cell types: nerve
cells (neurons) and two categories of non-neuronal
- Epithelial stem
cells in the lining of the digestive tract occur in deep
crypts and give rise to several cell types: absorptive
cells, goblet cells, paneth cells, and enteroendocrine
- Skin stem cells
occur in the basal layer of the epidermis and at the
base of hair follicles. The epidermal stem cells give
rise to keratinocytes, which migrate to the surface of
the skin and form a protective layer. The follicular
stem cells can give rise to both the hair follicle and
to the epidermis.
Transdifferentiation. A number of experiments have
reported that certain adult stem cell types can
differentiate into cell types seen in organs or tissues
other than those expected from the cells' predicted lineage
(i.e., brain stem cells that differentiate into blood cells
or blood-forming cells that differentiate into cardiac
muscle cells, and so forth). This reported phenomenon is
instances of transdifferentiation have been observed in some
vertebrate species, whether this phenomenon actually occurs
in humans is under debate by the scientific community.
Instead of transdifferentiation, the observed instances may
involve fusion of a donor cell with a recipient cell.
Another possibility is that transplanted stem cells are
secreting factors that encourage the recipient's own stem
cells to begin the repair process. Even when
transdifferentiation has been detected, only a very small
percentage of cells undergo the process.
In a variation of
transdifferentiation experiments, scientists have recently
demonstrated that certain adult cell types can be
"reprogrammed" into other cell types in vivo using a
well-controlled process of genetic modification (see Section
VI for a discussion of the principles of reprogramming).
This strategy may offer a way to reprogram available cells
into other cell types that have been lost or damaged due to
disease. For example, one recent experiment shows how
pancreatic beta cells, the insulin-producing cells that are
lost or damaged in diabetes, could possibly be created by
reprogramming other pancreatic cells. By "re-starting"
expression of three critical beta-cell genes in
differentiated adult pancreatic exocrine cells, researchers
were able to create beta cell-like cells that can secrete
insulin. The reprogrammed cells were similar to beta cells
in appearance, size, and shape; expressed genes
characteristic of beta cells; and were able to partially
restore blood sugar regulation in mice whose own beta cells
had been chemically destroyed. While not
transdifferentiation by definition, this method for
reprogramming adult cells may be used as a model for
directly reprogramming other adult cell types.
In addition to
reprogramming cells to become a specific cell type, it is
now possible to reprogram adult somatic cells to become like
embryonic stem cells (induced
pluripotent stem cells, iPSCs) through the
introduction of embryonic genes. Thus, a source of cells can
be generated that are specific to the donor, thereby
avoiding issues of histocompatibility, if such cells were to
be used for tissue regeneration. However, like embryonic
stem cells, determination of the methods by which iPSCs can
be completely and reproducibly committed to appropriate cell
lineages is still under investigation.
D. What are the key
questions about adult stem cells?
questions about adult stem cells remain to be answered. They
- How many kinds of
adult stem cells exist, and in which tissues do they
- How do adult stem
cells evolve during development and how are they
maintained in the adult? Are they "leftover" embryonic
stem cells, or do they arise in some other way?
- Why do stem cells
remain in an undifferentiated state when all the cells
around them have differentiated? What are the
characteristics of their ¡§niche¡¨ that controls their
- Do adult stem
cells have the capacity to transdifferentiate, and is it
possible to control this process to improve its
reliability and efficiency?
- If the beneficial
effect of adult stem cell transplantation is a trophic
effect, what are the mechanisms? Is donor cell-recipient
cell contact required, secretion of factors by the donor
cell, or both?
- What are the
factors that control adult stem cell proliferation and
- What are the
factors that stimulate stem cells to relocate to sites
of injury or damage, and how can this process be
enhanced for better healing?