Biomedical Engineering Reference
In-Depth Information
determination, the type of division changes to asymmetrical (Fig. 1C). During
asymmetric division one daughter cell remains a stem cell, while the second
daughter cell begins the process of differentiation into the mature tissue cells of
the developing fetus. In this way, the progeny of the totipotent embryonic stem
cells become tissue stem cells with more limited potential than embryonic cells,
and branches (lines) of cells are produced that formvarious differentiated organs.
Tissue-determined stem cells are retained during development and persist into
adult tissues, where they serve as reserve stem cells for normal tissue renewal (Sell,
2004a,b). Cancer as a cellular process is caused by a failure of the cells in the adult
tissues to mature normally (maturation arrest; Sell and Pierce, 1994), so that
instead of terminally differentiating to mature tissue cells, they retain the pro-
liferation potential of embryonic transit-amplifying cells.
1.1.1 Normal Tissue Renewal and Cancer
Normal tissue and cancer tissue contain the same populations of cells: stem
cells, transit-amplifying cells, and terminally differentiated cells (Pierce et al.,
1978; Sell, 2004a,b, 2006a; Sell and Pierce, 1994; Reya et al., 2001). Normal
tissue renewal and growth of cancer are both accomplished by division of the
transit-amplifying cells (Fig. 1C). Usually, the stem cells of both normal tissue
and cancers are relatively few in number, compared to the transit-amplifying
cells and the terminally differentiated cells, and they do not participate in
proliferation. The proliferating cells of both cancers and normal tissue are the
transit-amplifying cells. Cancer tissue differs from normal tissue in that the
transit-amplifying cells accumulate in cancer, whereas cells in normal tissue
differentiate so that they no longer divide (terminal differentiation).
1.1.2 Skin Cell Renewal
One of the best examples of the normal cellular lineage and also of the con-
tribution of maturation arrest to cancer is skin. The pluripotent skin epidermal
stem cells are located in the bulb of the hair follicle (Perez-Losada and Balmain,
2003). The epidermis-committed stem cells are located in the basal layer of the
skin (germinativum) and are much fewer in number than the transit-amplifying
cells located in the spinosum layer. Maturation is accomplished through the
accumulation of cytokeratin, which becomes prominent in the granular layer.
The granules contain cytokeratin. The cytoplasm of the cells in the granular
layer becomes filled with these granules and eventually the cells lose their
structure, forming the outer layer of acellular keratin, known as the corneum.
1.1.3 Skin Cancer
Skin cancers arise by maturation arrest at various levels of differentiation of the
epidermis (Fig. 2A; Perez-Losada and Balmain, 2003; Owens and Watt, 2003).
Maturation arrest of the primitive skin progenitor cells in the bulge of the hair
