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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(A)
irradiation blocks
all cell division
(B)
injection of a single
healthy neoblast
regeneration of
complete animal
all parts
can
regenerate
new clonal
animals
Figure 22–36 Regeneration of a
planarian from a single somatic cell.
(A) The distribution of dividing cells
(neoblasts, blue) in the adult body.
Irradiation blocks all cell division and
prevents regeneration, but (B) a single
unirradiated neoblast cell injected into the
irradiated animal is able to reconstitute
all tissues. This eventually produces a
complete animal that consists entirely
of the progeny of this one cell and can
regenerate. (Adapted from E.M. Tanaka
and P.W. Reddien, Dev. Cell 21:172–185,
2011.)
a whole amputated limb. In this process, differentiated cells seem to revert to an
embryonic character by first forming on the amputation stump a blastema—a
MBoC6 n22.109/22.36
small bud resembling an embryonic limb bud. The blastema then grows and its
cells differentiate to form a correctly patterned replacement for the limb that has
been lost, in what looks like a recapitulation of embryonic limb development (Figure
22–37). A large contribution to the blastema comes from the skeletal muscle
cells in the limb stump. These multinucleate cells re-enter the cell cycle, dedifferentiate,
and break up into mononucleated cells, which then proliferate within the
blastema, before eventually redifferentiating. But do they redifferentiate only into
muscle, or do they behave like neoblasts in the planarian and give rise to the full
range of cell types needed to reconstruct the missing part of the limb? Careful lineage
tracing, using genetic markers, shows (contrary to previous belief) that the
cells are restricted according to their origins: muscle-derived cells give rise only to
muscle, connective-tissue cells only to connective tissues, epidermal cells only to
epidermal cells. The cells in the adult vertebrate body are, after all, less adaptable
than the cells of the flatworm: by working in concert, they can replace the lost
structure, but each cell type is far from totipotent.
Why a newt can regenerate a whole limb—as well as many other body parts—
but a mammal cannot remains a profound mystery.
Stem Cells Can Be Used Artificially to Replace Cells That Are
Diseased or Lost: Therapy for Blood and Epidermis
Earlier in this chapter, we saw how mice can be irradiated to kill off their hematopoietic
cells, and then rescued by a transfusion of new stem cells, which repopulate
the bone marrow and restore blood cell production (see Figure 22–30). In the
same way, patients with some forms of leukemia or lymphoma can be irradiated
or chemically treated to destroy their cancerous cells along with the rest of their
hematopoietic tissue, and then can be rescued by a transfusion of healthy, noncancerous
hematopoietic stem cells. In favorable cases, these can be sorted out
from samples of the patient’s own hematopoietic tissue before it is ablated. They
are then transfused back afterward, avoiding problems of immune rejection.
AMPUTATION
REGENERATION
0 day 25 days
Figure 22–37 Newt limb regeneration.
The time-lapse sequence shows the stages
of regeneration after amputation at the level
of the humerus. The sequence spans the
events of wound healing, dedifferentiation
of stump tissues, blastema formation, and
redifferentiation. (Courtesy of Susan Bryant
and David Gardiner.)