Figure 22–35 The planarian worm, Schmidtea mediterranea. (a) external view. (b) immunostaining with three different antibodies, revealing the internal anatomy. (a, courtesy of a. Sánchez alvarado; b, from a. Sánchez alvarado, BMC Biol. 10:88, 2012.) injection of a single regeneration of healthy neoblast complete animal 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 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.
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.)
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.)