Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

REGENERation AND RepaiR
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Bcl2 promote the development of cancer in B lymphocytes. Indeed, the capacity
for unlimited self-renewal is a dangerous property for any cell to possess. Many
cases of leukemia arise through mutations that confer this capacity on committed
hematopoietic precursor cells that would normally be fated to differentiate and
die after a limited number of division cycles.
Summary
The many types of blood cells, including erythrocytes, lymphocytes, granulocytes,
and macrophages, all derive from a common multipotent stem cell. In the adult,
hematopoietic stem cells are found mainly in bone marrow, and they depend on signals
from the marrow stromal (connective-tissue) cells to maintain their stem-cell
character. The stem cells are few and far between, and they normally divide infrequently
to produce more stem cells (self-renewal) and various committed progenitor
cells (transit amplifying cells), each able to give rise to only one or a few types
of blood cells. The committed progenitor cells divide extensively under the influence
of various protein signal molecules (colony-stimulating factors, or CSFs) and then
terminally differentiate into mature blood cells, which usually die after several days
or weeks.
Studies of hematopoiesis have been greatly aided by in vitro assays in which
stem cells or committed progenitor cells form clonal colonies when cultured in a
semisolid matrix. The progeny of stem cells seem to make their choices between
alternative developmental pathways in a partly random manner. Cell death by
apoptosis, controlled by the availability of CSFs, also plays a central part in regulating
the numbers of mature differentiated blood cells.
Regeneration and Repair
As we have seen, many of the tissues of the body are not only self-renewing but
also self-repairing, and this is largely thanks to stem cells and the feedback controls
that regulate their behavior and maintain homeostasis. There are, however,
limits to what these natural repair mechanisms can achieve. In most parts of the
human brain, for example, nerve cells that die, as in Alzheimer’s disease, are not
replaced. Likewise, when heart muscle dies for lack of oxygen, as in a heart attack,
it is replaced by scar tissue rather than new heart muscle.
Some animals do far better than humans and can regenerate entire organs,
such as whole limbs, after amputation. Among the invertebrates, there are some
species that can even regenerate all the tissues of the body from a single somatic
cell. These phenomena encourage the hope that human cells might be coaxed by
artificial measures into similar feats of repair and regeneration, so as to replace
the skeletal muscle fibers that degenerate in victims of muscular dystrophy, the
nerve cells that die in patients with Parkinson’s disease, the insulin-secreting cells
that are lacking in type 1 diabetics, the heart muscle cells that die in a heart attack,
and so on. As we learn more about the basic cell biology, these goals, once only a
dream, are beginning to seem attainable.
In this section, we start with some examples of the remarkable regenerative
abilities of some animal species, as an indication of what is possible in principle.
We shall then discuss how we can improve upon the natural repair processes of
the human body and treat disease by exploiting the properties of the various types
of stem cells found in human tissues. In the final section of the chapter, we shall
see how a deeper understanding of the molecular biology of cell differentiation
and of stem cells has revealed ways to convert one type of cell into another, opening
up radically new possibilities.
Planarian Worms Contain Stem Cells That Can Regenerate a
Whole New Body
Schmidtea mediterranea is a small freshwater flatworm, or planarian, just under a
centimeter long when grown to full size (Figure 22–35). It has an epidermis, a gut,