Early development is characterized by the rapid proliferation of embryonic cells, which then differentiate to produce the many specialized types of cells that make up the tissues and organs of multicellular animals. As cells differentiate, their rate of proliferation usually decreases, and most cells in adult animals are arrested in the G0 stage of the cell cycle. A few types of differentiated cells never divide again, but most cells are able to resume proliferation as required to replace cells that have been lost as a result of injury or cell death. In addition, some cells divide continuously throughout life to replace cells that have a high rate of turnover in adult animals. Cell proliferation is thus carefully balanced with cell death to maintain a constant number of cells in adult tissues and organs.
Proliferation of Differentiated Cells
The cells of adult animals can be grouped into three general categories with respect to cell proliferation. A few types of differentiated cells, such as cardiac muscle cells in humans, are no longer capable of cell division. These cells are produced during embryonic development, differentiate, and are then retained throughout the life of the organism. If they are lost because of injury [e.g., the death of cardiac muscle cells during a heart attack], they can never be replaced.
In contrast, most cells in adult animals enter the G0 stage of the cell cycle but resume proliferation as needed to replace cells that have been injured or have died. Cells of this type include skin fibroblasts, smooth muscle cells, the endothelial cells that line blood vessels, and the epithelial cells of most internal organs, such as the liver, pancreas, kidney, lung, prostate, and breast. One example of the controlled proliferation of these cells, discussed earlier in this chapter, is the rapid proliferation of skin fibroblasts to repair damage resulting from a cut or wound. Another striking example is provided by liver cells, which normally divide only rarely. However, if large numbers of liver cells are lost [e.g., by surgical removal of part of the liver], the remaining cells are stimulated to proliferate to replace the missing tissue. For example, surgical removal of two-thirds of the liver of a rat is followed by rapid cell proliferation, leading to regeneration of the entire liver within a few days.
Stem Cells
Other types of differentiated cells, including blood cells, epithelial cells of the skin, and the epithelial cells lining the digestive tract, have short life spans and must be replaced by continual cell proliferation in adult animals. In these cases, the fully differentiated cells do not themselves proliferate. Instead, they are replaced via the proliferation of cells that are less differentiated, called []. Stem cells divide to produce daughter cells that can either differentiate or remain as stem cells, thereby serving as a source for the production of differentiated cells throughout life.
Figure 14.43
Stem cell proliferation. Stem cells divide to form one daughter cell that remains a stem cell and a second that differentiates [e.g., to an intestinal epithelial cell].
A good example of the continual proliferation of stem cells is provided by blood cell differentiation. There are several distinct types of blood cells with specialized functions: Erythrocytes [red blood cells] transport O2 and CO2; granulocytes and macrophages are phagocytic cells; platelets [which are fragments of megakaryocytes] function in blood coagulation; and lymphocytes are responsible for the immune response. All these cells have limited life spans, ranging from less than a day to a few months, and are continually produced by the division of a common stem cell [the pluripotent stem cell] in the bone marrow []. Descendants of the pluripotent stem cell then become committed to specific differentiation pathways. These cells continue to proliferate and undergo several rounds of division as they differentiate. Once they become fully differentiated, however, they cease proliferation, so the maintenance of differentiated blood cell populations is dependent on continual proliferation of the pluripotent stem cell.
Figure 14.44
Formation of blood cells. All of the different types of blood cells develop from a pluripotent stem cell in the bone marrow. The precursors of differentiated cells undergo several rounds of cell division as they mature, but cell proliferation ceases at [more...]
Because stem cells can replicate as well as differentiating to give rise to a variety of cell types, they are of considerable interest with respect to potential medical applications. For example, it may be possible to use stem cells to treat human diseases and repair damaged tissues. The stem cells with the broadest differentiative capacity are the embryonal stem cells [ES cells] that are present in early embryos and can give rise to all of the differentiated cell types of adult organisms. As discussed in Chapter 3, these cells can be cultured from mouse embryos and used to introduce altered genes into mice [see ]. In 1998, two groups of researchers reported the isolation of ES cells from human embryos, raising the possibility that these human stem cells could be used for medical applications. Notably, this advance followed the first demonstration, in 1997, that the nucleus of an adult cell could give rise to a viable animal [in this case, a lamb] following transplantation into an oocyte. It is thus theoretically possible that the nucleus of an adult human cell could be used to give rise to ES cells, which could then provide a source of tissue for treatment of that individual. In addition, stem cells have been isolated from adult tissues that give rise not only to blood cells but also to many other cell types, including neurons and cells of connective tissues such as bone, cartilage, fat, and muscle. Therapeutic applications of these adult stem cells may avoid the ethical issues associated with the use of embryos as a source of ES cells. Continuing research on stem cells may thus open new approaches to the treatment of a broad array of human diseases.