© 1998 American Heart Association, Inc.
Point/Counterpoint |
Ventricular Myocytes Are Not Terminally Differentiated in the Adult Mammalian Heart
From the Department of Medicine, New York Medical College, Valhalla.
Key Words: cell proliferation • cell death • insulin-like growth factor-1 • cell cycle
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Terminally Differentiated Cells |
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Primary cultures of various cell types contain dividing and nondividing cells.1 2 However, nondividing cells can rest in the G0 phase and reenter the cell cycle on stimulation3 4 5 or become terminally differentiated and die without dividing.6 This third category of cells is not dormant in G0 and cannot reenter the cell cycle.6 For example, such a phenomenon is present in vivo at the tip of the villi of the small intestine,7 in the auditory hair cells of the ear,8 and in the upper layers of the epidermis.9 In contrast, hepatocytes in vivo are in a G0 state,10 11 12 and after partial hepatectomy or severe injury, liver regeneration is accomplished by proliferation of mature hepatocytes as well as biliary epithelial cells and fenestrated endothelial cells.12 The reconstitution of liver mass is not dependent on a reserve of stem cells, which condition regeneration of bone marrow13 and skin.14 Multipotential cells have also been identified in the central nervous system, but their ability to grow, differentiate, and ultimately survive has been problematic.15 In skeletal muscle, satellite cells can be stimulated to proliferate and develop into mature myocytes, representing an additional form of tissue regeneration.16 17 18 These mechanisms of cellular growth have not been considered possible in adult cardiac myocytes, and the concept was advanced that no proliferation of ventricular muscle cells occurs once cell division has ceased, shortly after birth in the mammalian heart.19
The dogma was introduced that adult cardiac myocytes are terminally
differentiated cells and, therefore, cannot be recalled into the cell
cycle.20 21 These
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