Breaking the rules of cell biology: Lessons from the liver's exceptional regenerative capacity

The inability of most human organs to regenerate themselves after injury underlies the lifelong morbidity of numerous diseases. As we continue to seek solutions for these intractable conditions, the liver emerges as an inspiring and informative exception. The liver is the only solid organ that can completely regenerate itself. At the core of this extraordinary feat of organ physiology lie two equally exceptional features of cell biology. First, liver regeneration is driven not by stem cells, but rather by the proliferation of the liver's differentiated cells. Second, many of these liver cells are polyploid, yet still able to execute proper cell division. Understanding how liver cells maintain proliferative capacity as differentiated cells and how they execute mitosis faithfully in a polyploid state could offer powerful insights toward engineering regenerative capacity in other organs. The liver thus offers not only proof that mammalian organ regeneration is possible, but also a blueprint for achieving this long-standing goal of regenerative medicine.