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.
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, 0.2 mm pharynx a brain, a pair of primitive eyes, a peripheral nervous system, musculature, and excretory and reproductive organs—most of the basic body parts familiar in other animals, although all relatively simple by vertebrate standards and built from about 20–25 distinct differentiated cell types. For more than a century, planarians such as Schmidtea have intrigued biologists because of their extraordinary capacity for regeneration: a small tissue fragment taken from almost any part of the body will reorganize itself and grow to form a complete new animal. This property goes with another: when the animal is starved, it gets smaller and smaller, by reducing its cell numbers while maintaining essentially normal body proportions. This behavior is called degrowth, and it can continue until the animal is as little as one-twentieth or even a smaller fraction of its full size. Supplied with food, it will grow back to full size again. Cycles of degrowth and growth can be repeated indefinitely, without impairing survival or fertility.
Underlying this behavior is a process of continual cell turnover. Along with the differentiated cells, which do not divide, there is a population of small, apparently undifferentiated dividing cells called neoblasts. The neoblasts constitute about 20% of the cells in the body and are widely distributed within it; by cell division, they serve as stem cells for the production of new differentiated cells. Differentiated cells, meanwhile, are continually dying by apoptosis, allowing their corpses to be phagocytosed and digested by neighboring cells. Through this cell cannibalism, the constituents of the dying cells can be efficiently recycled. Cell birth continues in a dynamic balance with cell death and cell cannibalism, no matter whether the animal is fed or starved. In conditions of starvation, the balance is evidently tilted toward cell cannibalism, and in conditions of plenty, toward cell birth.
A high dose of x-rays halts all cell division, puts a stop to cell turnover, and destroys the capacity for regeneration. The result is death after a delay of several weeks. The animal can be rescued, however, by injecting into it a single neoblast isolated from an unirradiated donor (Figure 22–36). In a certain proportion of cases, the injected cell divides to form a clone of progeny that eventually repopulate the entire body, creating a healthy regenerative individual with an apparently complete set of differentiated cell types as well as dividing neoblasts. Genetic markers prove that these are all derived from the single neoblast that was injected. It follows that at least some neoblasts are totipotent (or at least highly pluripotent) stem cells; that is, cells able to give rise to all (or at least almost all) of the cell types that make up the body of a flatworm, including more neoblasts like themselves.
One might think that such powers of regeneration would be a prerogative of small, simple, primitive animals. But some vertebrates, too, especially fish and amphibians, show remarkable regenerative abilities. A newt, for example, can regenerate