celldeath terpse

This regeneration is mediated by proliferation of

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Unformatted text preview: ly quiescent, arrested in the G0 phase of the cell cycle, but are activated to proliferate in response to injury or exercise. Once activated, the satellite cells give rise to progeny that undergo several divisions and then differentiate and fuse to form new muscle fibers. The continuing capacity of skeletal muscle to regenerate throughout life is due to selfrenewal of the satellite stem cell population. Stem cells have also been found in many other adult tissues, including the brain and heart, and it is possible that most--if not all--tissues contain stem cells with the potential of replacing cells that are lost during the lifetime of the organism. It appears that stem cells reside within distinct microenvironments, called niches, which provide the environmental signals that maintain stem cells throughout life and control the balance between their self-renewal and differentiation. Stem cells are rare in adult mammalian tissues, however, so the precise identification of stem cells and their niches represents a major challenge in the field of stem cell biology. For example, although the role of stem cells in maintenance of the intestinal epithelium has long been recognized, the intestinal stem cells at the base of the crypt (see Figure 17.19) were only recently identified by studies of Hans This material cannot be copied, reproduced, manufactured, or disseminated in any form without express written permission from the publisher. 2009 Sinauer Associates, Inc. UNCORRECTED PAGE PROOFS CELL DEATH AND CELL RENEWAL 21 (A) (B) Nucleus of muscle fiber One muscle fiber (muscle cell) Satellite cell Myofibril Nucleus of muscle fiber FIGURE 17.21 Muscle satellite cells (A) The stem cells of skeletal muscle are the satellite cells, located beneath the basal lamina of muscle fibers. (B) Electron micrograph showing a satellite cell and the nucleus of a muscle fiber. (From S. Charg and M. Rudnicki, 2003. Physiol. Rev. 84: 209; courtesy of Sophie Charg and Michael Rudnicki.) Satellite cell Plasma membrane Myofibril Basal lamina Clever and his colleagues in 2007. Signaling by the Wnt pathway (see Figure 15.44) plays a major role in controlling the proliferation of these stem cells, and it is thought that Wnt polypeptides secreted by fibroblasts of the underlying connective tissue are responsible for intestinal stem cell maintenance. Wnt signaling is also involved in regulation of several other types of stem cells, including stem cells of the skin and hematopoietic system. In addition, signaling by the TGF-b, Hedgehog, and Notch pathways (see Figures 15.41, 15.43, and 15.45) play important roles in stem cell regulation, although the precise roles of these factors in regulating different types of stem cells within their distinct niches remains to be understood. Medical Applications of Adult Stem Cells The ability of adult stem cells to repair damaged tissue clearly suggests their potential utility in clinical medicine. If these stem cells could be isolated and propagated in culture, they could in principal be used to replace damaged tissue and treat a variety of disorders, such as diabetes or degenerative diseases like muscular dystrophy, Parkinson's or Alzheimer's disease. In some cases, the use of stem cells derived from adult tissues may be the optimal approach for such stem cell therapies, although the use of embryonic stem cells (discussed in the next section of this chapter) is likely to provide a more versatile approach to treatment of a wider variety of disorders. A well-established clinical application of adult stem cells is hematopoietic stem cell transplantation (or bone marrow transplantation), which plays an important role in the treatment of a variety of cancers. As discussed in Chapter 18, most cancers are treated by chemotherapy with drugs that kill rapidly dividing cells by damaging DNA or inhibiting DNA replication. These drugs do not act selectively against cancer cells but are also This material cannot be copied, reproduced, manufactured, or disseminated in any form without express written permission from the publisher. 2009 Sinauer Associates, Inc. UNCORRECTED PAGE PROOFS 22 CHAPTER 17 FIGURE 17.22 Hematopoietic stem cell transplantation A cancer patient is treated with high doses of chemotherapy, which effectively kill tumor cells but normally would not be tolerated because of potentially lethal damage to the hematopoietic system. This damage is then repaired by transplantation of new hematopoietic stem cells. High dose chemotherapy Hematopoietic stem cell transplant Tumor Cancer patient Drugs kill tumor cells Toxicity to hematopoietic system Restoration of hematopoietic system Stored umbilical cord blood from an unrelated donor can also be used as a source of hematopoietic stem cells for transplantation. toxic to those normal tissues that are dependent on continual renewal by stem cells, such as blood, skin, hair, and the intestinal epithelium. The hematopoietic stem cells are among the most rapidly dividing cells of the body, so t...
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